Augmented Calcium Currents in Mesenteric Artery Branches of the Spontaneously Hypertensive Rat

Abstract

Abstract The greater efficacy of organic channel blockers in lowering peripheral resistance and blood pressure in hypertensive subjects has been suggested to be the result of augmented calcium influx through L-type calcium channels in arterial smooth muscle. These studies were performed to determine whether differences exist in voltage-gated calcium channels of mesenteric artery branches from 20-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Single myocytes were acutely isolated by collagenase and elastase treatment and studied at room temperature (≈20°C) with the use of whole-cell, patch-clamp methods. Maximum values of calcium current measured at 0 mV from a holding potential of −90 mV were larger in SHR myocytes (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) myocytes. 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 maximum calcium current at holding potentials of −60 and −40 mV in SHR compared with WKY myocytes: for example, at −40 mV calcium current was reduced 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 groups was completely superimposed. Difference currents were calculated by subtracting currents measured from holding potentials of −90 and −40 mV. The voltage dependence of difference currents was identical to that of the calcium currents measured from the two values of holding potential. The results of this study indicate that (1) only L-type calcium currents are present in freshly isolated mesenteric artery myocytes from 20-week-old WKY and SHR, and (2) these currents are larger in SHR. These differences in calcium currents may contribute to augmented contractile responses that have been previously reported.