Rat aortic smooth muscle cells expressing charybdotoxin-sensitive potassium channels exhibit enhanced proliferative responses.
1. The relationship between the expression of potassium (K+) channels and the growth properties of cultured vascular smooth muscle cells was examined. 2. Two groups of cells having different proliferative rates were cultured from the Wistar-Kyoto rat aorta. One group of cells, derived from early passages (3-5), proliferated with a cell doubling time of 2.41 days. A second group of cells, derived from late passages (> 12), proliferated at a higher rate (cell doubling time, 0.61 days). 3. Exposure of the early passaged cells to endothelin-1 (0.1 mumol/L) induced membrane depolarization. In contrast, exposure of the late passage cells to endothelin-1 (0.1 mumol/L) evoked a rapid hyperpolarization. The hyperpolarization in the late passage cells was blocked by charybdotoxin (20 nmol/L), an inhibitor of the large-conductance Calcium (Ca)-activated K+ channel. 4. The authors conclude that rapidly proliferating vascular smooth muscle cells express enhanced activity of Ca-activated K+ channels causing marked alterations in the electrical properties of the cells. It is therefore suggested that the reported increase in Ca-activated K+ channel activity in the aortae of hypertensive rats is likely to be associated with the increased proliferative ability of the vascular smooth muscle cells.
Neylon
C B
CB
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Avdonin
P V
PV
Larsen
M A
MA
Bobik
A
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018999:Charybdotoxin; D016232:Endothelins / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology*
D016232:Endothelins; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D002118:Calcium