Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA

Abstract

THERE are dihydropyridine (DHP)-sensitive calcium currents in both skeletal and cardiac muscle cells, although the properties of these currents are very different in the two cell types¹ (for simplicity, we refer to currents in both tissues as L-type¹²). The mechan-isms of depolarization-contraction coupling also differ. As the predominant voltage-dependent calcium current of cardiac cells¹, the L-type current represents a major pathway for entry of extra-cellular calcium. This entry triggers the subsequent large release of calcium from the sarcoplasmic reticulum (SR) ^3–5. In contrast, depolarization of skeletal muscle releases calcium from the SR^6,7 without the requirement for entry of extracellular calcium through L-type calcium channels^8,9. To investigate the molecular basis for these differences in calcium currents and in excitation-contraction (?–C) coupling, we expressed complementary DNAs for the DHP receptors from skeletal¹⁰ and cardiac muscle¹¹ in dysgenic skeletal muscle. We compared the properties of the L-type channels pro-duced and showed that expression of a cardiac calcium channel in skeletal muscle cells results in ?–C coupling resembling that of cardiac muscle.