Characterization of stretch-activated cation current in coronary smooth muscle cells

Stretch-activated ion currents were recorded from vascular smooth muscle (V SM) after enzymatic isolation of single cells from porcine coronary arterio les. Patch pipettes were used to record whole cell current and control cell length. Under voltage clamp in physiological saline solution, an inward ca tion current (I-CAT) was activated by 105-135% longitudinal stretch. I-CAT coincided with an increase in intracellular Ca2+ concentration. Under curre nt clamp, membrane depolarization was induced by stretch. The magnitude of I-CAT varied from -0.8 to -6.9 pA/pF at a holding potential of -60 mV. I-CA T was graded with stretch, inactivated on release, and could be repeatedly induced. A potassium current (I-K) activated in unstretched cells by depola rization was also enhanced by stretch. In Ca2+-free bath solution, stretch- induced enhancement of I-K was blocked, but I-CAT was still present. Hexame thyleneamiloride (50 muM), a reputed inhibitor of mechanosensitive channels , blocked I-CAT and the stretch-induced increase in I-K but not basal I-K. Grammostolla spatulata venom (1: 100,000) blocked basal I-K, blocked stretc h-induced increases in I-K, and blocked I-CAT. Iberiotoxin, a specific Ca2-activated K+ channel blocker, did not alter I-CAT but blocked the stretch- induced increase in I-K and increased the magnitude of stretch-induced depo larization. We concluded that longitudinal stretch directly activates a cat ion current and secondarily activates a Ca2+ activated K+ current in isolat ed coronary myocytes. Although these two currents would partially counterac t each other, the predominance of I-CAT at physiological potentials is like ly to explain the depolarization and contraction observed in intact coronar y VSM during pressure elevation.