Acid–induced currents in freshly isolated cerebral artery smooth muscle cells are predominately conducted by ASIC1b

Abstract

Our laboratory has demonstrated the presence of acid‐sensing ion channels (ASIC)‐like currents in freshly isolated cerebral vascular smooth muscle cells (VSMC). In these cells, extracellular H+ (pH≤6.5) induces an amiloride‐sensitive inward Na+ current. However, the ASIC subunits mediating this response are unknown. In this study, Western blotting and immunostaining demonstrated robust expression of ASIC1b, although other subunits were also detected to a lesser extent. Patchclamp was utilized to determine if ASIC1b may mediate H+‐gated currents; we evaluated responses to psalmotoxin 1 (PcTX1, 100nM), a known inhibitor and activator of ASIC1a and ASIC1b channels, respectively. In voltage‐clamped VSMCs, PcTX1 inhibited H+‐induced (pH 6.0) inward current in only 4 of 44 VSMCs examined. PcTX1 enhanced currents in 34/44 VSMCs by 12.0±2.7 pA/pF (p<0.001) and increased the mean desensitization constant of the initial decline phase of peak current (2.2±0.3 to 4.7±0.9 s; p<0.05; n=15). Taken together, these findings suggest that ASIC1b conducts most H+ gated currents in freshly isolated VSMC.