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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/2/L271    most recent 00020.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Jernigan, N. L. Articles by Resta, T. C. PubMed PubMed Citation Articles by Jernigan, N. L. Articles by Resta, T. C.

ASIC1 contributes to pulmonary vascular smooth muscle store-operated Ca²⁺ entry

Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico

Submitted 21 January 2009 ; accepted in final form 27 May 2009

Acid-sensing ion channels (ASIC) are voltage-insensitive, cationic channels that have recently been identified in vascular smooth muscle (VSM). It is possible that ASIC contribute to vascular reactivity via Na⁺ and Ca²⁺ conductance; however, their function in VSM is largely unknown. In pulmonary VSM, store-operated Ca²⁺ entry (SOCE) plays a significant role in vasoregulatory mechanisms such as hypoxic pulmonary vasoconstriction and receptor-mediated arterial constriction. Therefore, we hypothesized that ASIC contribute to SOCE in pulmonary VSM. We examined SOCE resulting from depletion of intracellular Ca²⁺ stores with cyclopiazonic acid in isolated small pulmonary arteries and primary cultured pulmonary arterial smooth muscle cells by measuring 1) changes in VSM [Ca²⁺]_i using fura-2 indicator dye, 2) Mn²⁺ quenching of fura-2 fluorescence, and 3) store-operated Ca²⁺ and Na⁺ currents using conventional whole cell patch-clamp configuration in voltage-clamp mode. The role of ASIC was assessed by the use of the ASIC inhibitors, amiloride, benzamil, and psalmotoxin 1, or siRNA directed towards ASIC1, ASIC2, or ASIC3 isoforms. We found that store-operated VSM [Ca²⁺]_i responses, Mn²⁺ influx, and inward cationic currents were attenuated by either pharmacological ASIC inhibition or treatment with ASIC1 siRNA. These data establish a unique role for ASIC1 in mediating SOCE in pulmonary VSM and provide new insight into mechanisms of VSM Ca²⁺ entry and pulmonary vasoregulation.

degenerin/epithelial Na⁺ channel; pulmonary hypertension; calcium current; capacitative calcium entry; sodium current; psalmotoxin 1; vascular reactivity