Involvement of the calcium inward current in cardiac impulse propagation: induction of unidirectional conduction block by nifedipine and reversal by Bay K 8644.
In general, the fast sodium inward current (INa) is regarded as the main inward current ensuring fast and safe excitation of the normally polarized working myocardium. However, under conditions of locally delayed excitation in the millisecond range, the slow inward current (ICa) might additionally contribute to the success of impulse propagation. This hypothesis was tested in patterned growth cultures of neonatal rat ventricular myocytes, which consisted of narrow cell strands connected to large rectangular cell monolayers, where INa or ICa could be modified in the narrow cell strand adjacent to the expansion by a microsuperfusion system. As assessed during antegrade (strand-->expansion) propagation under control conditions using a system for multiple site optical recording of transmembrane voltage (MSORTV), this cell pattern gave either rise to local activation delays at the expansion ranging from 0.5 to 4 ms (dcontrol), or it induced undirectional conduction blocks (UCBs) in the antegrade direction. Irrespective of the size of dcontrol, suppression of the sodium current with tetrodotoxin confined to the cell strand adjacent to the expansion invariably induced UCB in the antegrade direction. If dcontrol was > 1 ms, UCB could also be elicited by suppression of ICa alone with nifedipine. Conversely, if UCB was present under control conditions, the inclusion of Bay K 8644 in the microsuperfusion established successful bidirectional conduction. These results suggest that ICa can be critically important for the success of impulse propagation across abrupt expansions of excitable tissue even if INa is not concurrently depressed.
Rohr
S
S
Department of Physiology, University of Bern, Switzerland. rohr@pyl.unibe.ch
Kucera
J P
JP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008858:Microscopy, Phase-Contrast; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium