Effects of a calcium entry promoting 1,4,5,7-tetrahydro-furo[3,4-b] pyridine derivative on Na+-, Ca2+- and Mg2+-dependent bioelectrical activity of Purkinje fibres and papillary muscles.
4-(2-Difluoromethoxyphenyl)-2-methyl-5-oxo-1,4,5,7-tetrahydro- furo[3,4-b]pyridine-3-carboxylic acid ether ester (CGP 28 392), a dihydropyridine derivative with an annellated lactone ring, was examined in automatically discharging calf Purkinje fibres. Velocity of spontaneous depolarization during both the early and the late phase of the diastolic pause and the rate of rise of the action potential were increased, with the threshold potential at which the upstroke is generated being unaltered. These findings are discussed in terms of ionic mechanisms, including in particular the contribution of sodium ions during the late phase of the diastolic depolarization and the novel type of calcium channel which is supposed to contribute to pacemaker depolarization and action potential initiation. In general, the effects of equimolar concentrations of nifedipine were opposite to those of CGP 28 392. At 1 X 10(-5) mol/l, however, both CGP 28 392 and nifedipine accelerated the late phase of diastolic depolarization. In electrically stimulated, partially depolarized guinea-pig papillary muscles, CGP 28 392 also prolonged the slow action potential and markedly increased inotropism. In equimolar concentrations nifedipine shortened the slow action potential and inhibited contractility. The effects of CGP 28 392 are thus compatible with facilitation of calcium entry and--in Purkinje fibres--also with enhancement of fast sodium conductivity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008274:Magnesium / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D007473:Ion Channels; D011725:Pyridines; D013779:Tetrodotoxin; C040525:CGP 28392; D012964:Sodium; D008274:Magnesium; D002118:Calcium