L-type calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats: effects of calcium agonist and antagonist.
Studies using the whole-cell voltage-clamp technique have demonstrated that L-type Ca2+ channel activity is increased in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). We recorded L-type Ca2+ channel currents in cultured mesenteric artery smooth muscle cells from SHR and Wistar Kyoto (WKY) rats by using the cell-attached patch-clamp technique. Depolarizing voltage steps from a holding potential of -40 mV elicited voltage-dependent inward Ba2+ currents. There was no difference in the L-type Ca2+ channel I-V curve or in the open probability between SHR and WKY. The inward currents were inhibited by the Ca2+ antagonists nifedipine and verapamil, but were enhanced by the Ca2+ agonist Bay K 8644 in a concentration-dependent manner. The Bay K 8644-induced increase and the nifedipine-induced inhibition of the inward currents were enhanced in SHR, whereas there was no difference in the verapamil-induced inhibition of the currents between the two strains of rats. These results suggest that the enhanced L-type Ca2+ channel activity observed in vascular smooth muscle cells from SHR is not due to altered function of a single L-type Ca2+ channel. It appears that the sensitivity of dihydropyridine receptors in the channels is enhanced in SHR.
Kubo
T
T
Department of Pharmacology, Showa College of Pharmaceutical Sciences, Machida, Japan.
Taguchi
K
K
Ueda
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000737:chemistry / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000166:cytology; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014700:Verapamil / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine