AUGMENTED CALCIUM CURRENTS IN MESENTERIC-ARTERY BRANCHES OF THE SPONTANEOUSLY HYPERTENSIVE RAT

The greater efficacy of organic channel blockers in lowering periphera l resistance and blood pressure in hypertensive subjects has been sugg ested to be the result of augmented calcium influx through L-type calc ium channels in arterial smooth muscle. These studies were performed t o determine whether differences exist in voltage-gated calcium channel s of mesenteric artery branches from 20-week-old spontaneously hyperte nsive rats (SHR) compared with Wistar-Kyoto rats (WKY). Single myocyte s were acutely isolated by collagenase and elastase treatment and stud ied at room temperature (approximate to 20 degrees C) with the use of whole-cell, patch-clamp methods. Maximum values of calcium current mea sured al 0 mV from a holding potential of -90 mV were larger in SHR my ocytes (105+/-11 versus 149+/-15 pA). Values of cell capacitance were smaller in SHR (29.5+/-1.3 pF) compared with WKY (35.0+/-1.5 pF) myocy tes. Cell capacitance measures surface membrane area and, when used to normalize calcium currents, magnified the difference between WKY and SHR to approximately 47%. There was a larger percent reduction of maxi mum calcium current at holding potentials of -60 and -40 mV in SHR com pared with WKY myocytes: for example, at -40 mV calcium current was re duced from values at -90 mV by -73+/-2% in SHR compared with -58+/-1% in WKY. When divided by the maximum current for each holding potential , the voltage dependence of normalized calcium currents for the two gr oups was completely superimposed. Difference currents were calculated by subtracting currents measured from holding potentials of -90 and -4 0 mV. The voltage dependence of difference currents was identical to t hat of the calcium currents measured from the two values of holding po tential. The results of this study indicate that (1) only L-type calci um currents are present in freshly isolated mesenteric artery myocytes from 20-week-old WKY and SHR, and (2) these currents are larger in SH R. These differences in calcium currents may contribute to augmented c ontractile responses that have been previously reported.