Ca2+ channel inactivation in small mesenteric arteries of WKY and SHR.
BACKGROUND
This study was designed to test the hypothesis that differences exist in the inactivation properties of voltage-gated Ca(2+) channels (Ca(V)) in hypertensive arterial smooth muscle cells (ASMCs), and that these differences contribute to enhanced Ca(V) activity.


METHODS
The properties of Ca(V) were studied in freshly isolated myocytes from small mesenteric arteries (SMAs) of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) using whole-cell patch-clamp methods.


RESULTS
Peak currents (I(Ca)) were larger in SHR with either 2 mmol/l Ca(2+) or Ba(2+) as the charge carrier. In WKY and SHR, the peak current was larger with Ba(2+) than with Ca(2+) with no difference in their ratio. The voltage dependence of Ca(V) activation was shifted to the left in SHR as compared to WKY for Ca(2+) but not for Ba(2+), while availability was not different. The time course of inactivation of current could be represented by two time constants, both of which were larger in SHR than in WKY and also larger for Ba(2+) than for Ca(2+), with a greater fraction of inactivation being associated with the process slower in SHR and with Ba(2+). The time courses of availability, inactivation, and recovery from inactivation were faster in SHR than in WKY in the case of Ca(2+), but there was no difference in the case of Ba(2+).


CONCLUSIONS
These results demonstrate that there are differences between WKY and SHR in the inactivation properties of SMA Ca(V), and that these differences could contribute to larger steady-state currents. The differences cannot be explained merely by the presence of a larger number of identical Ca(V) complexes, and it appears likely that differences in intrinsic compositions, primary structures, and/or regulation are involved.
Cox
Robert H
RH
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, USA. coxr@mlhs.org
Lozinskaya
Irina M
IM
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032342:Muscle Cells / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015220:Calcium Channels