Endothelin induces a nonselective cation current in vascular smooth muscle cells.
The potent vasoconstrictor endothelin leads to smooth muscle cell depolarization and increases in intracellular Ca2+. Although effects of endothelin on calcium channels have been described, it also has been speculated that endothelim may activate additional ion channels. The purpose of the present study was to identify an alternative ion current that could play a role in depolarizing cells in response to vasoconstrictors like endothelin and vasopressin. The effects of endothelin, vasopressin, sarafotoxin S6b, and phenylephrine were assessed using whole-cell patch-clamp recordings from primary dissociated rat aortic or mesenteric arterial smooth muscle cells cultured for 24-72 hours. From the usual resting potentials of these cells of -50 to -60 mV, endothelin (1-100 nM) induced a depolarization via an increase in membrane conductance. This depolarization was phasic, oscillating repeatedly from the resting potential to a relatively depolarized level and back to the resting potential. From a holding potential of -60 mV, endothelin-1, endothelin-3, vasopressin, or sarafotoxin S6b (but not phenylephrine) induced transient inward currents that also could be phasic. In external sodium, lithium, or cesium (but not Tris) and in internal potassium or cesium, these currents reversed near 0 mV. Although nifedipine-insensitive, the inward currents were absent in zero calcium, barium, or strontium, or in the presence of cobalt or nickel. These results represent the first report of a nonselective cation current in primary vascular smooth muscle cells that is calcium dependent and that could be responsible for the depolarizations induced from the resting potential by vasoconstrictors such as endothelin.
Chen
C
C
Department of Analytical Pharmacology, Glaxo Research Institute, Research Triangle Park, N.C.
Wagoner
P K
PK
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016232:Endothelins; D007473:Ion Channels; D014662:Vasoconstrictor Agents; D002118:Calcium