AJP - Lung Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 294: L1007-L1012, 2008. First published March 14, 2008; doi:10.1152/ajplung.00171.2007
1040-0605/08 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
294/5/L1007    most recent
00171.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, M.
Right arrow Articles by Murray, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, M.
Right arrow Articles by Murray, P. A.

Differential effects of intravenous anesthetics on capacitative calcium entry in human pulmonary artery smooth muscle cells

Mikyung Yang, Xueqin Ding, and Paul A. Murray

Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio; and Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Submitted 27 April 2007 ; accepted in final form 12 March 2008


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We assessed the roles of the protein kinase C (PKC) and the tyrosine kinase (TK) signaling pathways in regulating capacitative calcium entry (CCE) in human pulmonary artery smooth muscle cells (PASMCs) and investigated the effects of intravenous anesthetics (midazolam, propofol, thiopental, ketamine, etomidate, morphine, and fentanyl) on CCE in human PASMCs. Fura-2-loaded human PASMCs were placed in a dish (37°C) on an inverted fluorescence microscope. Intracellular Ca2+ concentration ([Ca2+]i) was measured as the 340/380 fluorescence ratio in individual PASMCs. Thapsigargin, a sarcoplasmic reticulum Ca2+-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+. CCE was then activated by restoring extracellular Ca2+ (2.2 mM). The effects of PKC activation and inhibition, TK inhibition, and the intravenous anesthetics on CCE were assessed. Thapsigargin caused a transient increase in [Ca2+]i. Restoring extracellular Ca2+ caused a rapid peak increase in [Ca2+]i, followed by a sustained increase in [Ca2+]i; i.e., CCE was stimulated in human PASMCs. PKC activation attenuated (P < 0.05), whereas PKC inhibition potentiated (P < 0.05), both peak and sustained CCE. TK inhibition attenuated (P < 0.05) both peak and sustained CCE. Midazolam, propofol, and thiopental each attenuated (P < 0.05) both peak and sustained CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE. Our results suggest that CCE in human PASMCs is influenced by both the TK and PKC signaling pathways. Midazolam, propofol, and thiopental each attenuated CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE.

protein kinase C; tyrosine kinase

INTRAVENOUS ANESTHETICS ARE widely used in anesthetic practice as premedicants, induction agents, or main anesthetics in total intravenous anesthesia. In general, intravenous anesthetic agents have been shown to exert a pulmonary vasodilator influence (24, 28). Modulation of intracellular calcium concentration ([Ca2+]i) is a key factor in the regulation of vascular smooth muscle tone. Capacitative calcium entry (CCE) is activated by depletion of intracellular Ca2+ stores (3, 27). It is a critical mechanism for refilling intracellular Ca2+ stores and maintaining a sustained increase in [Ca2+]i (5, 20). CCE is a possible cellular target for anesthetic agents that alter vascular smooth muscle tone (11). CCE has been demonstrated in human pulmonary artery smooth muscle cells (HPASMCs) (16), although the mechanism by which CCE regulates vascular smooth muscle tone in HPASM is unknown. Moreover, the effects of intravenous anesthetics on CCE have not been elucidated.

We have previously demonstrated that the protein kinase C (PKC) and tyrosine kinase (TK) signaling pathways are involved in CCE in canine PASMCs (11, 18), whereas only TK is involved in CCE in canine pulmonary venous smooth muscle cells (PVSMCs) (30). Moreover, we have reported that intravenous anesthetics attenuate CCE via the PKC signaling pathway in canine PASMCs (18) and via the TK signaling pathway in canine PVSMCs (30). The goal of the current study was to investigate the effects of intravenous anesthetics on CCE in HPASMCs and to assess the roles of the PKC and TK signaling pathways in regulating CCE.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
All procedures were approved by the Cleveland Clinic Institutional Animal Care and Use Committee (Cleveland, OH).

Cell culture of HPASMCs. To initiate cultures, cryopreserved HPASMCs (Cascade Biologics, Portland, OR) were thawed and inoculated in 25-cm2 culture flasks (Becton Dickinson Labware, Franklin Lakes, NJ). Cells were nourished by Medium 231(Cascade Biologics) containing Smooth Muscle Growth Supplement (Cascade Biologics) and antibiotic mixture solution (10,000 U/ml penicillin and 10,000 µg/ml streptomycin; Life Technologies, Rockville, MD). Cells were kept in a humidified atmosphere of 5% CO2-95% air at 37°C and were allowed to proliferate for 7–10 days until confluence was achieved. Cells were then subcultured to 35-mm culture dishes specially designed for fluorescence microscopy (Bioptechs {Delta}T System, Butler, PA) and used for experimentation within 72 h after subculture. Cells from the third passage were used for experiments.

Fura-2 loading procedure. Twenty-four hours before experimentation, the culture medium containing 10% fetal bovine serum was replaced with serum-free medium to arrest cell growth, allow for establishment of steady-state cellular events independent of cell division, and to prevent a false estimate of [Ca2+]i resulting from binding of available dye to serum protein in the medium. HPASMCs were loaded with the acetoxymethyl ester form of fura-2 (fura-2-AM: 2 µM) at ambient temperature. After the 30-min loading period, the cells were washed twice in Krebs-Ringer buffer, which contained 125 mM NaCl, 5 mM KCl, 1.2 mM MgSO4, 11 mM glucose, 2.5 mM CaCl2, and 25 mM HEPES, at pH 7.40 adjusted with NaOH at ambient temperature for an additional 20 min before initiating the study. This provided enough time to wash away any extracellular fura-2-AM and for intracellular esterases to cleave fura-2-AM into the active fura-2.

Determination of intracellular free calcium concentration. Culture dishes containing fura-2-loaded HPASMCs were placed in a temperature-regulated (37°C) chamber (Bioptechs) mounted on the stage of an Olympus IX-70 inverted fluorescence microscope (Olympus America, Lake Success, NY). Fluorescence measurements were performed on individual HPASMCs in a cultured monolayer using a dual wavelength spectrofluorometer (Deltascan RFK6002; Photon Technology International, So. Brunswick, NJ) at excitation wavelengths of 340 and 380 nm and an emission wavelength of 510 nm. The volume of the chamber was 1.5 ml. The cells were bathed with Krebs-Ringer buffer. The temperature of all solutions was maintained at 37°C in a water bath. Solution changes were accomplished rapidly by aspirating the buffer in the dish and infusing new solution. Just before data acquisition, background fluorescence (i.e., fluorescence between cells) was measured and subtracted automatically from the subsequent experimental measurements. Fura-2 fluorescence signals (340, 380, and 340/380 ratio) originating from single HPASMCs were continuously monitored at a sampling frequency of 25 Hz and were collected using a software package from Photon Technology International. [Ca2+]i was measured as the 340/380 fluorescence ratio in individual HPASMCs.

Experimental protocols. Thapsigargin (1 µM), a sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor (33), was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+. CCE was induced when extracellular Ca2+ (2.2 mM) was restored. Any given HPASMC was exposed to only one agent. The effects of L-type voltage-dependent Ca2+ channel inhibition (nifedipine: 10 µM), nonselective Ca2+ channel inhibition (SKF-96365: 50 µM), TK inhibition (Tyrphostin 23: 100 µM), PKC activation (phorbol 12-myristate 13-acetate; PMA, 1 µM), and PKC inhibition (bisindolylmaleimide 1; BIS1, 1 µM) on CCE were investigated. The concentration of each inhibitor was chosen based on previous experience in PASMCs (11, 18) and PVSMCs (9, 10). The effects of intravenous anesthetics [midazolam (100 µM), propofol (100 µM), thiopental (100 µM), ketamine (100 µM), etomidate (100 µM), morphine (100 µM), and fentanyl (1 µM)] on CCE were also assessed.

Reagents. Midazolam and morphine were purchased from Baxter Healthcare (Deerfield, IL). Tyrphostin 23, thiopental, thapsigargin, and nifedipine were obtained from Sigma Chemical (St. Louis, MO), propofol from Aldrich (Milwaukee, WI), ketamine from Fort Dodge Animal Health (Fort Dodge, IA), and etomidate and fentanyl from Abbott Laboratories (N. Chicago, IL). BIS1, PMA, and SKF-96365 were obtained from Calbiochem (La Jolla, CA), and fura-2-AM was purchased from Teflabs (Austin, TX). Etomidate, fentanyl, ketamine, midazolam, and morphine were dissolved in distilled water as stock solutions. BIS1, fura-2-AM, nifedipine, propofol, PMA, SKF-96365, thapsigargin, and Tyrphostin 23 were dissolved in DMSO (Sigma Chemical) as stock solutions. Aliquots of each stock solution were diluted 1:1,000 in Krebs-Ringer buffer to achieve final concentrations. Similar dilutions of DMSO in Krebs-Ringer buffer had no effect on [Ca2+]i (10). Pure propofol was used to avoid any effects of the intralipid emulsion on the fluorescence signal.

Data analysis. The peak and sustained 340/380 fluorescence signals were measured when the solution was switched from a Ca2+-free solution to a solution containing 2.2 mM Ca2+. Triplicate CCE responses were measured in each cell. The peak ratio was obtained by reading the highest point of the trace. The sustained ratio was obtained by averaging the fluorescence values measured 5 min after reintroduction of the Ca2+-containing solution. The change in the 340/380 fluorescence ratio was then calculated by subtracting the resting ratio value (baseline) of each intervention. Changes in the peak and sustained ratio in response to the agents are expressed as percent of control. The control response was the first CCE response in each cell, and this value was set at 100%. Data are expressed as means ± SE. Statistical analysis utilized repeated measures analysis of variance and Student's t-test for intra- and intergroup comparison, respectively. Differences were considered statistically significant at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
CCE in HPASMCs. CCE was triggered by thapsigargin-induced depletion of intracellular Ca2+ stores. Thapsigargin stimulated a transient increase in [Ca2+]i by releasing Ca2+ from SR Ca2+ stores. After [Ca2+]i had returned to baseline, the extracellular Ca2+ concentration ([Ca2+]o) was restored (2.2 mM) in the continued presence of thapsigargin. Restoring [Ca2+]o caused a rapid peak increase in [Ca2+]i (242 ± 24%), followed by a sustained increase in [Ca2+]i (186 ± 13%), i.e., CCE was stimulated in HPASMCs (Fig. 1A). To assess the reproducibility of inducing CCE in the same HPASMC, extracellular Ca2+ was sequentially removed and restored three consecutive times in the continued presence of thapsigargin. There were no significant differences in the peak or sustained increases in [Ca2+]i between the first and the second CCE, but the third CCE was slightly smaller (P < 0.05) in magnitude in the peak and sustained increases in [Ca2+]i compared with the first CCE (Fig. 1B). In all subsequent experiments, the second CCE response in paired untreated HPASMCs was compared with the second CCE response in HPASMCs pretreated with either an inhibitor, an activator, or an intravenous anesthetic.


Figure 1
View larger version (20K):
[in this window]
[in a new window]

  		Fig. 1. A: representative trace depicting capacitative calcium entry (CCE) after depletion of sarcoplasmic reticulum Ca2+ stores with thapsigargin. Extracellular Ca2+ (2.2 mM) was sequentially added and removed 3 times. Adding extracellular Ca2+ caused a peak and sustained increase in intracellular Ca2+ concentration. B: summarized data showing the reproducibility of the CCE response. The third CCE response was slightly smaller in magnitude compared with the first CCE. *P < 0.05 compared with the first CCE (n = 11 cells).

 
Effect of voltage-operated Ca2+ channel inhibition on CCE. Nifedipine was used to inhibit voltage-dependent Ca2+ channels. Nifedipine (10 µM) was applied 5 min before [Ca2+]o was restored the second time (Fig. 2A). As expected, nifedipine had no effect on the peak or sustained increases in [Ca2+]i due to CCE (Fig. 2B).


Figure 2
View larger version (16K):
[in this window]
[in a new window]

  		Fig. 2. A: representative trace depicting effect of voltage-gated L-type Ca2+ channel blocker, nifedipine (10 µM), on CCE. B: summarized data showing that nifedipine had no effect on CCE (n = 6 cells).

 
Effect of receptor-operated Ca2+ channel inhibition on CCE. SKF-96365 is a nonselective Ca2+ channel inhibitor that has been used by many investigators to inhibit CCE (34). SKF-96365 (50 µM) was applied 5 min before [Ca2+]o was restored the second time (Fig. 3A). SKF-96365 attenuated (P < 0.05) peak and sustained CCE by 79 ± 2% and 73 ± 2%, respectively (Fig. 3B).


Figure 3
View larger version (12K):
[in this window]
[in a new window]

  		Fig. 3. A: representative trace depicting effect of nonselective Ca2+ channel blocker (SKF-96365; 50 µM) on CCE. B: summarized data showing inhibitory effect of SKF-96365 on CCE. *P < 0.05 compared with untreated (n = 8 cells).

 
Effects of PKC activation and inhibition on CCE. PMA (1 µM) and BIS1 (1 µM) were used to activate and inhibit PKC, respectively. They were applied 5 min before [Ca2+]o was restored the second time. The PKC activator PMA (1 µM) attenuated (P < 0.05) peak and sustained CCE (Fig. 4A), whereas PKC inhibition with BIS1 (1 µM) slightly potentiated (P < 0.05) peak and sustained CCE (Fig. 4B).


Figure 4
View larger version (13K):
[in this window]
[in a new window]

  		Fig. 4. A: summarized data showing inhibitory effect of protein kinase C activation (PMA; 1 µM) on CCE. *P < 0.05 compared with untreated (n = 9 cells). B: summarized data showing potentiating effect of protein kinase C inhibition (BIS1; 1 µM) on CCE. *P < 0.05 compared with untreated (n = 8 cells).

 
Effect of TK inhibition on CCE. Tyrphostin 23 was used to inhibit TK. Tyrphostin 23 (100 µM) was applied 5 min before [Ca2+]o was restored the second time. Tyrphostin 23 attenuated (P < 0.05) peak and sustained CCE (Fig. 5).


Figure 5
View larger version (10K):
[in this window]
[in a new window]

  		Fig. 5. Summarized data showing inhibitory effect of tyrosine kinase inhibition (Tyrphostin 23; 100 µM) on CCE. *P < 0.05 compared with untreated (n = 9 cells).

 
Effects of intravenous anesthetics on CCE. The intravenous anesthetics were applied 15 min before [Ca2+]o was restored the second time. Midazolam (100 µM), propofol (100 µM), and thiopental (100 µM) each attenuated (P < 0.05) both peak and sustained CCE (Fig. 6). However, ketamine (100 µM), etomidate (100 µM), morphine (100 µM), and fentanyl (1 µM) each failed to attenuate peak or sustained CCE (Fig. 7 and 8).


Figure 6
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 6. A: summarized data showing inhibitory effect of midazolam (100 µM) on CCE. *P < 0.05 compared with untreated (n = 9 cells). B: summarized data showing inhibitory effect of propofol (100 µM) on CCE. *P < 0.05 compared with untreated (n = 9 cells). C: summarized data showing inhibitory effect of thiopental (100 µM) on CCE. *P < 0.05 compared with untreated (n = 10 cells).

 

Figure 7
View larger version (15K):
[in this window]
[in a new window]

  		Fig. 7. A: summarized data showing that ketamine (100 µM) had no effect on CCE (n = 11 cells). B: summarized data showing that etomidate (100 µM) had no effect on CCE (n = 8 cells).

 

Figure 8
View larger version (16K):
[in this window]
[in a new window]

  		Fig. 8. A: summarized data showing that morphine (100 µM) had no effect on CCE (n = 6 cells). B: summarized data showing that fentanyl (1 µM) had no effect on CCE (n = 7 cells).

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The main findings of this study are as follows. First, both PKC and TK are involved in the signal transduction pathway for CCE in HPASMCs. The TK signaling pathway positively regulates CCE, whereas PKC negatively regulates CCE. Second, intravenous anesthetics have differential effects on CCE. Midazolam, thiopental, and propofol attenuate CCE, whereas ketamine, etomidate, morphine, and fentanyl have no effect on CCE.

Regulation of [Ca2+]i is vital for vascular smooth muscle function. Increases in [Ca2+]i lead to activation of myosin light chain kinase and phosphorylation of the 20-kDa light chains of myosin (MLC20) (12). MLC20 phosphorylation allows the binding of myosin to actin, which increases actomyosin adenosinetriphosphatase (ATPase) activity and causes vascular smooth muscle contraction (31). Agonist-induced changes in [Ca2+]i usually consist of initial Ca2+ release from the SR, followed by sustained Ca2+ entry though sarcolemmal Ca2+ channels. Depletion of SR Ca2+ due to agonist-induced Ca2+ release triggers Ca2+ influx though store-operated Ca2+ channels in the plasma membrane, namely CCE (26). Therefore, CCE is a mechanism that links [Ca2+]SR (calcium concentration in the sarcoplasmic reticulum) to membrane Ca2+ permeability (5, 20) and serves as an important pathway to refill intracellular Ca2+ stores and maintain sustained Ca2+ influx (20). In the current study, thapsigargin was used as a tool to deplete the SR pool of Ca2+ in the absence of extracellular Ca2+ and thereby activate CCE. Consistent with our previous studies (18, 30), the amplitude of the thapsigargin-induced increase in [Ca2+]i was variable, which likely reflects differences in the size of the SR store in different cells. A number of studies have indicated that the contractile response to SR Ca2+-ATPase inhibitors in smooth muscle is caused by Ca2+ entry through both voltage-operated calcium channels (VOCCs) and store-operated calcium channels (SOCCs); the relative contribution of each depends on the smooth muscle type (14), with SOCCs appearing to be of greater importance in tonic smooth muscle, such as found in the gastric fundus and pulmonary artery (14). In this study, the L-type VOCC blocker, nifedipine, had no effect on CCE, whereas SKF-96365 markedly attenuated both the peak and sustained increases in [Ca2+]i due to CCE. These results suggest that CCE is insensitive to voltage-gated Ca2+ channel inhibitors in HPASMCs.

The mechanism linking store depletion to the opening of SOCCs remains elusive. It might involve the generation of a diffusible chemical messenger or a direct protein-protein interaction between the SR and the plasma membrane (14). It is well established that PKC regulates many aspects of Ca2+ signaling. These include inhibition of IP3 production (4, 13, 17), thereby inhibiting hormone-dependent Ca2+ release and facilitation (6, 25) or inhibition (21, 22, 25) of CCE. In the present study, activation of PKC with PMA attenuated both peak and sustained CCE. In contrast, PKC inhibition with BIS1 potentiated both peak and sustained CCE. Thus, PKC negatively regulates CCE in HPASMCs.

Besides PKC, tyrosine phosphorylation has been reported to modulate CCE in a variety of cells (11, 21, 22, 29, 30). It has been reported that depletion of intracellular Ca2+ stores triggers tyrosine phosphorylation (29), and inhibition of TK attenuates CCE in a number of cell types (2, 32), including smooth muscle (8). We have demonstrated that inhibition of TK attenuates CCE in canine PASMCs and PVSMCs (18, 30). Consistent with these previous studies, the TK inhibitor Tyrphostin 23 attenuated CCE in HPASMCs. This suggests that the TK signaling pathway is involved in CCE in HPASMCs. Together, these results suggest that CCE in HPASMCs involves both PKC and TK pathways.

Two studies have investigated CCE in HPASMCs (15, 19). One of them demonstrated that CCE is an important mechanism required to maintain the elevated [Ca2+]i and stored [Ca2+] in HPASMCs via a novel gene family, transient receptor potential (TRP) genes. It has been reported that TRP-encoded proteins may be the putative channels responsible for CCE (5, 7). Moreover, PKC and TK have been shown to regulate the phosphorylation of TRP (1, 23). Therefore, PKC and TK may regulate CCE in HPASMCs via regulating the phosphorylation of TRP.

Because CCE is involved in the regulation of [Ca2+]i and vasomotor tone in PASMCs (11), the ion channel associated with CCE may serve as a cellular target for intravenous anesthetics. We previously demonstrated that propofol attenuated CCE in canine PASMCs via a PKC-dependent mechanism (18), and thiopental, midazolam, and ketamine each attenuated CCE in canine PVSMCs via a TK-dependent mechanism (30). However, the effects of intravenous anesthetics on CCE in human pulmonary arterial smooth muscle have not been investigated. In the present study, midazolam, propofol, and thiopental each attenuated CCE, whereas etomidate, ketamine, morphine, and fentanyl had no effect on CCE in HPASMCs. The cellular target for the intravenous anesthetics-induced attenuation of CCE remains to be elucidated, although possible mechanisms could involve inhibition of expression of TRP, as well as the PKC and/or TK signaling pathways.

We acknowledge that results obtained from this in vitro study can only be cautiously extrapolated to clinical practice. However, because CCE is an important mechanism for regulating vascular smooth muscle contraction, our results provide new insight concerning the effects of intravenous anesthetics on human pulmonary arterial smooth muscle contraction. CCE should be considered as a possible cellular target for anesthetic agents that alter vascular smooth muscle tone.

In summary, CCE exists in HPASMCs. The PKC signaling pathway negatively regulates CCE, whereas the TK signaling pathway positively regulates CCE. Midazolam, propofol, and thiopental each attenuate CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE in HPASMCs. We will investigate the cellular mechanism by which the intravenous anesthetics attenuated CCE in HPASMCs in future studies.


   FOOTNOTES
 

Address for reprint requests and other correspondence: P. A. Murray, Center for Anesthesiology Research, NE63, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195 (e-mail: murrayp{at}ccf.org)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB. Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. J Biol Chem 279: 20941–20949, 2004.[Abstract/Free Full Text]
  2. Aptel HB, Burnay MM, Rossier MF, Capponi AM. The role of tyrosine kinases in capacitative calcium influx-mediated aldosterone production in bovine adrenal zona glomerulosa cells. J Endocrinol 163: 131–138, 1999.[Abstract]
  3. Berridge MJ. Capacitative calcium entry. Biochem J 312: 1–11, 1995.[Web of Science][Medline]
  4. Bird GS, Rossier MF, Obie JF, Putney JW Jr. Sinusoidal oscillations in intracellular calcium requiring negative feedback by protein kinase C. J Biol Chem 268: 8425–8428, 1993.[Abstract/Free Full Text]
  5. Birnbaumer L, Zhu X, Jiang M, Boulay G, Peyton M, Vannier B, Brown D, Platano D, Sadeghi H, Stefani E, Birnbaumer M. On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins. Proc Natl Acad Sci USA 93: 15195–15202, 1996.[Abstract/Free Full Text]
  6. Bode HP, Goke B. Protein kinase C activates capacitative calcium entry in the insulin secreting cell line RINm5F. FEBS Lett 339: 307–311, 1994.[CrossRef][Web of Science][Medline]
  7. Boulay G, Brown DM, Qin N, Jiang M, Dietrich A, Zhu MX, Chen Z, Birnbaumer M, Mikoshiba K, Birnbaumer L. Modulation of Ca2+ entry by polypeptides of the inositol 1,4,5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca2+ entry. Proc Natl Acad Sci USA 96: 14955–14960, 1999.[Abstract/Free Full Text]
  8. Burt RP, Chapple CR, Marshall I. The role of capacitative Ca2+ influx in the alpha 1B-adrenoceptor-mediated contraction to phenylephrine of the rat spleen. Br J Pharmacol 116: 2327–2333, 1995.[Web of Science][Medline]
  9. Ding X, Murray PA. Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins. Am J Physiol Lung Cell Mol Physiol 289: L825–L833, 2005.[Abstract/Free Full Text]
  10. Ding X, Murray PA. Regulation of pulmonary venous tone in response to muscarinic receptor activation. Am J Physiol Lung Cell Mol Physiol 288: L131–L140, 2005.[Abstract/Free Full Text]
  11. Doi S, Damron DS, Horibe M, Murray PA. Capacitative Ca2+ entry and tyrosine kinase activation in canine pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 278: L118–L130, 2000.[Abstract/Free Full Text]
  12. Driska SP, Aksoy MO, Murphy RA. Myosin light chain phosphorylation associated with contraction in arterial smooth muscle. Am J Physiol Cell Physiol 240: C222–C233, 1981.[Abstract/Free Full Text]
  13. Drummond AH. Bidirectional control of cytosolic free calcium by thyrotropin-releasing hormone in pituitary cells. Nature 315: 752–755, 1985.[CrossRef][Medline]
  14. Gibson A, McFadzean I, Wallace P, Wayman CP. Capacitative Ca2+ entry and the regulation of smooth muscle tone. Trends Pharmacol Sci 19: 266–269, 1998.[CrossRef][Medline]
  15. Golovina VA. Cell proliferation is associated with enhanced capacitative Ca2+ entry in human arterial myocytes. Am J Physiol Cell Physiol 277: C343–C349, 1999.[Abstract/Free Full Text]
  16. Golovina VA, Platoshyn O, Bailey CL, Wang J, Limsuwan A, Sweeney M, Rubin LJ, Yuan JX. Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation. Am J Physiol Heart Circ Physiol 280: H746–H755, 2001.[Abstract/Free Full Text]
  17. Hepler JR, Earp HS, Harden TK. Long-term phorbol ester treatment down-regulates protein kinase C and sensitizes the phosphoinositide signaling pathway to hormone and growth factor stimulation. Evidence for a role of protein kinase C in agonist-induced desensitization. J Biol Chem 263: 7610–7619, 1988.[Abstract/Free Full Text]
  18. Horibe M, Kondo I, Damron DS, Murray PA. Propofol attenuates capacitative calcium entry in pulmonary artery smooth muscle cells. Anesthesiology 95: 681–688, 2001.[CrossRef][Web of Science][Medline]
  19. Mauban JR, Wilkinson K, Schach C, Yuan JX. Histamine-mediated increases in cytosolic Ca2+ involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. Am J Physiol Cell Physiol 290: C325–C336, 2006.[Abstract/Free Full Text]
  20. McDaniel SS, Platoshyn O, Wang J, Yu Y, Sweeney M, Krick S, Rubin LJ, Yuan JX. Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 280: L870–L880, 2001.[Abstract/Free Full Text]
  21. Montero M, Garcia-Sancho J, Alvarez J. Inhibition of the calcium store-operated calcium entry pathway by chemotactic peptide and by phorbol ester develops gradually and independently along differentiation of HL60 cells. J Biol Chem 268: 26911–26919, 1993.[Abstract/Free Full Text]
  22. Montero M, Garcia-Sancho J, Alvarez J. Phosphorylation down-regulates the store-operated Ca2+ entry pathway of human neutrophils. J Biol Chem 269: 3963–3967, 1994.[Abstract/Free Full Text]
  23. Odell AF, Scott JL, Van Helden DF. Epidermal growth factor induces tyrosine phosphorylation, membrane insertion, and activation of transient receptor potential channel 4. J Biol Chem 280: 37974–37987, 2005.[Abstract/Free Full Text]
  24. Park WK, Lynch C III, Johns RA. Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. Anesthesiology 77: 956–963, 1992.[CrossRef][Web of Science][Medline]
  25. Petersen CC, Berridge MJ. The regulation of capacitative calcium entry by calcium and protein kinase C in Xenopus oocytes. J Biol Chem 269: 32246–32253, 1994.[Abstract/Free Full Text]
  26. Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium 7: 1–12, 1986.[CrossRef][Web of Science][Medline]
  27. Putney JW Jr. Capacitative calcium entry revisited. Cell Calcium 11: 611–624, 1990.[CrossRef][Web of Science][Medline]
  28. Rich GF, Roos CM, Anderson SM, Daugherty MO, Uncles DR. Direct effects of intravenous anesthetics on pulmonary vascular resistance in the isolated rat lung. Anesth Analg 78: 961–966, 1994.[Abstract/Free Full Text]
  29. Sargeant P, Farndale RW, Sage SO. Calcium store depletion in dimethyl BAPTA-loaded human platelets increases protein tyrosine phosphorylation in the absence of a rise in cytosolic calcium. Exp Physiol 79: 269–272, 1994.[Abstract]
  30. Shimizu S, Ding X, Murray PA. Intravenous anesthetics inhibit capacitative calcium entry in pulmonary venous smooth muscle cells. Anesthesiology 104: 791–797, 2006.[CrossRef][Web of Science][Medline]
  31. Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature 372: 231–236, 1994.[CrossRef][Medline]
  32. Takemura H, Sakano S, Kaneko M, Ohshika H. Inhibitory effects of tyrosine kinase inhibitors on capacitative Ca2+ entry in rat glioma C6 cells. Life Sci 62: L271–L276, 1998.
  33. Thastrup O, Cullen PJ, Drobak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc Natl Acad Sci USA 87: 2466–2470, 1990.[Abstract/Free Full Text]
  34. Wayman CP, McFadzean I, Gibson A, Tucker JF. Two distinct membrane currents activated by cyclopiazonic acid-induced calcium store depletion in single smooth muscle cells of the mouse anococcygeus. Br J Pharmacol 117: 566–572, 1996.[Web of Science][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
294/5/L1007    most recent
00171.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, M.
Right arrow Articles by Murray, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, M.
Right arrow Articles by Murray, P. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.