The enhanced L-type calcium channel activity in spontaneously hypertensive rats appears to be driven by increased sensitivity of dihydropyridine receptors rather than altered single-channel function.
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 et al. (1998) studied this question.