Elevated density and altered pharmacologic properties of myocardial calcium current of the spontaneously hypertensive rat

DESIGN: The membrane current mediated by the L-type calcium channel (ICa) was studied for myocytes isolated from the ventricle of 10- to 11-week-old spontaneously hypertensive rats (SHR). RESULTS: Compared with age-matched normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats, the amplitude of ICa was greater for the SHR. Two observations suggest that the greater ICa of the SHR was not due to hypertrophy. First, the similarity of membrane capacitance for these three strains of rat indicated lack of hypertrophy. Secondly, the amplitude of ICa was also greater for myocytes isolated from the right ventricle of the SHR. The ICa of the SHR was more sensitive to drugs known to activate calcium channels via phosphorylation. Specifically, extracellular application of 1 mumol/l isoprenaline as well as intracellular dialysis with either 1 mmol/l cyclic AMP or with 1 mmol/l adenosine 5'-O-3-thiotriphosphate increased the mean ICa of SHR myocytes significantly more than that of WKY rat cells. The ICa of SHR myocytes was also more sensitive to BAY K 8644 and its enantiomorphs. CONCLUSION: The present data suggest that the greater peak amplitude of ICa for SHR myocytes relative to that of myocytes of normotensive rats is due to an increase in current density and enhancement of channel phosphorylation.