Calcium sparks, BK and SK channels regulate myogenic tone in the gerbil spiral modiolar artery

Abstract

Ca2+ sparks and large‐conductance Ca2+‐ and voltage‐dependent K+ (BK) channels hyperpolarize and relax vascular smooth muscle cells leading to vasodilation. In this study, we elucidate the role of Ca2+ sparks and BK channels in the vasoregulation of the gerbil spiral modiolar artery (SMA). Pressurized (60 cmH2O) SMA exhibited Ca2+ sparks with a frequency of 0.9 ± 0.1 Hz. Spark frequency was unchanged from 20 to 60 cmH2O, but increased two‐fold between 60 and 80 cmH2O. Ryanodine (10 μM) abolished Ca2+ sparks and increased cytosolic Ca2+ at both 40 and 60 cmH2O. The effect of ryanodine on vascular diameter was pressure‐dependent. Ryanodine robustly constricted arteries pressurized at 40 cmH2O. In contrast, ryanodine had negligible effect on diameter of arteries at 60 or 80 cmH2O, where spark frequency was highest. However, when arteries at 60 cmH2O were first briefly exposed to endothelin‐1 (1 nM), an agent that increases Ca2+ sensitivity of smooth muscle cells, ryanodine caused a vasoconstriction. Iberiotoxin (100 nM), an inhibitor of BK channels, had no effect on vascular diameter, but elicited a robust constriction in the presence of apamin (100 nM), a blocker of small conductance Ca2+‐activated K+ (SK) channels. The results indicate that the myogenic tone of the SMA is regulated by Ca2+ sparks, BK and SK channels as well as the Ca2+‐sensitivity of the smooth muscle cells of the spiral modiolar artery. (NIH R01‐DC04280)