Characterization of stretch-activated cation current in coronary smooth muscle cells.
Stretch-activated ion currents were recorded from vascular smooth muscle (VSM) after enzymatic isolation of single cells from porcine coronary arterioles. Patch pipettes were used to record whole cell current and control cell length. Under voltage clamp in physiological saline solution, an inward cation current (I(CAT)) was activated by 105--135% longitudinal stretch. I(CAT) coincided with an increase in intracellular Ca(2+) concentration. Under current 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(CAT) was graded with stretch, inactivated on release, and could be repeatedly induced. A potassium current (I(K)) activated in unstretched cells by depolarization was also enhanced by stretch. In Ca(2+)-free bath solution, stretch-induced enhancement of I(K) was blocked, but I(CAT) was still present. Hexamethyleneamiloride (50 microM), 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 stretch-induced increases in I(K), and blocked I(CAT). Iberiotoxin, a specific Ca(2+)-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 depolarization. We concluded that longitudinal stretch directly activates a cation current and secondarily activates a Ca(2+)-activated K(+) current in isolated coronary myocytes. Although these two currents would partially counteract each other, the predominance of I(CAT) at physiological potentials is likely to explain the depolarization and contraction observed in intact coronary VSM during pressure elevation.
Department of Medical Physiology, Texas A & M University System Health Science Center, College Station, Texas 77843, USA.
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D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D013552:Swine
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C057360:5-(N,N-hexamethylene)amiloride; D001030:Apamin; C064719:iberiotoxin; D000584:Amiloride; D002118:Calcium