Adaptational process of the cardiac Ca2+ channels to pressure overload: biochemical and physiological properties of the dihydropyridine receptors in normal and hypertrophied rat hearts.

Inotropic responsiveness to dihydropyridines (DHP) and characterization of DHP receptors were studied during the onset of hypertrophy in rat hearts. The inotropic responsiveness of isolated hearts to external Ca2+ (0.25-2.50 mM) and nifedipine (10(-9)-10(-7) M), as expressed in percent change in dP/dtmax, was unchanged by the process of hypertrophy. Characterization of DHP receptors by Scatchard plots (Kd = 0.45 and 0.47 nM for nitrendipine), displacement curves (Kd = 0.44 and 0.42 nM for PN 200-110), and dissociation kinetics (k-1 = 4.82 X 10(-2) X min-1 and 4.85 X 10(-2) X min-1) revealed the similarity of the Ca2+ antagonist binding sites in hypertrophied and control hearts, respectively. These results on crude or purified sarcolemmal preparations from left ventricle were consistent with the presence of only one type of binding site of high affinity for DHP. The total number of Ca2+ channels was increased in hypertrophied left ventricle (LV) as compared with left ventricle from sham-operated animals (15,000 fmol/LV and 8900 fmol/LV), respectively. This increased synthesis of Ca2+ channels was observed as early as 5 days after the aortic stenosis and was related to the increase in ventricular mass. Results are in favor of an adaptational process of regulation of the total number of Ca2+ channels as an answer to pressure overload.