Different effects of calcium-antagonists on automaticity in single pacemaker cells and in synchronized networks of cultured embryonic heart muscle cells.
The inhibitory effects of the calcium antagonists D-600 and diltiazem on impulse formation of pacemaker cells were studied in embryonic chick heart cells, cultured either as single cells or as synchronized multicellular networks. Our findings show that D-600 and diltiazem inhibit the spontaneous action potentials of the cultured cells in a potential- and use-dependent way. However, a marked reduction of the beat frequency could not be found during inactivation of the spontaneous action potentials in the single cells. Only in synchronized multicellular networks cultured under the same conditions was the beat frequency clearly reduced, probably due to the ability of Ca-antagonists to inactivate the most quickly discharging cells first. Thus, the dominant pacemaker cell in a synchronized multicellular network will fade out first and the subsequent negative chronotropic effect is the outcome of a shift in the pacemaker center to cells with a lower intrinsic frequency. These findings indicate that Ca-antagonists predominantly inhibit excitability and impulse conduction. The velocity of slow diastolic depolarization of the single pacemaker cell is not markedly decreased and, therefore, cannot be used to explain the process behind the negative chronotropic effects seen in multicellular systems.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004110:Diltiazem / Q000494:pharmacology*; D004553:Electric Conductivity; D004558:Electric Stimulation; D005711:Gallopamil / Q000494:pharmacology; D008954:Models, Biological; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D001552:Benzazepines; D002121:Calcium Channel Blockers; D005711:Gallopamil; D004110:Diltiazem