Minor contribution of cytosolic Ca^sub 2+^ transients to the pacemaker rhythm in guinea pig sinoatrial node cells

The question of the extent to which cytosolic ... affects sinoatrial node pacemaker activity has been discussed for decades. We examined this issue by analyzing two mathematical pacemaker models, based on the "... clock" (C) and "membrane clock" (M) hypotheses, together with patc...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2011-01, Vol.300 (1), p.H251
Main Authors: Himeno, Yukiko, Toyoda, Futoshi, Satoh, Hiroyasu, Amano, Akira, Cha, Chae Young, Matsuura, Hiroshi, Noma, Akinori
Format: Article
Language:English
Subjects:
Calcium
Cells
Computer based modeling
Membranes
Rodents
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Summary:The question of the extent to which cytosolic ... affects sinoatrial node pacemaker activity has been discussed for decades. We examined this issue by analyzing two mathematical pacemaker models, based on the "... clock" (C) and "membrane clock" (M) hypotheses, together with patch-clamp experiments in isolated guinea pig sinoatrial node cells. By applying lead potential analysis to the models, the C mechanism, which is dependent on potentiation of ... exchange current via spontaneous ... release from the sarcoplasmic reticulum (SR) during diastole, was found to overlap M mechanisms in the C model. Rapid suppression of pacemaker rhythm was observed in the C model by chelating intracellular ..., whereas the M model was unaffected. Experimental rupturing of the perforated-patch membrane to allow rapid equilibration of the cytosol with 10 mM BAPTA pipette solution, however, failed to decrease the rate of spontaneous action potential within ~30 s, whereas contraction ceased within ~3 s. The spontaneous rhythm also remained intact within a few minutes when SR ... dynamics were acutely disrupted using high doses of SR blockers. These experimental results suggested that rapid disruption of normal ... dynamics would not markedly affect spontaneous activity. Experimental prolongation of the action potentials, as well as slowing of the ...-mediated inactivation of the L-type ... currents induced by BAPTA, were well explained by assuming ... chelation, even in the proximity of the channel pore in addition to the bulk cytosol in the M model. Taken together, the experimental and model findings strongly suggest that the C mechanism explicitly described by the C model can hardly be applied to guinea pig sinoatrial node cells. The possible involvement of L-type ... current rundown induced secondarily through inhibition of .../calmodulin kinase II and/or ...-stimulated adenylyl cyclase was discussed as underlying the disruption of spontaneous activity after prolonged intracellular ... concentration reduction for >5 min. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0363-6135
1522-1539