A possible mechanism for large stretch-induced increase in [Ca2+]i in isolated guinea-pig ventricular myocytes.
OBJECTIVE
The aim of the study was to investigate the mechanisms responsible for provoking and maintaining a large, stretch-induced, increase in the level of resting calcium in single guinea-pig ventricular myocytes. In particular, we wished to test the relative importance of intracellular and extracellular sources of calcium in this phenomenon.


METHODS
Carbon fibres were used to stretch cells loaded with the fluorescent calcium indicator Indo-1. Sarcomere length and internal calcium activity ([Ca2+]i) were measured. Experimental results from our present and previous studies were compared with those predicted by the OXSOFT HEART (version 4) model of the guinea-pig ventricular myocyte incorporating a stretch-activated channel.


RESULTS
The stretch-induced increase in [Ca2+]i was found to be sensitive to removal of [Ca2+]o and application of the Ca(2+)-channel blocker verapamil (1 microM). The phenomenon was not sensitive to disruption of sarcoplasmic reticulum function by ryanodine (1 microM) nor to the Na+ channel blocker TTX (30 microM). Our experimental findings were reproduced in the modelling study.


CONCLUSIONS
The stretch-induced increase in [Ca2+]i is modulated by extracellular sources of Ca2+ rather than intracellular Ca2+ stores and is not indiscriminately sensitive to blockers of depolarizing current. We propose that the stretch-induced increase in [Ca2+]i may be triggered by activation of stretch-activated channels but that a combination of stretch-activated current and Ca(2+)-window current maintain the increased levels of resting [Ca2+]i.
Gannier
F
F
Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, CNRS EP 21, Faculté des Sciences, Tours, France.
White
E
E
Garnier
Le Guennec
J Y
JY
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D003198:Computer Simulation; D006168:Guinea Pigs; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013314:Stress, Mechanical; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015222:Sodium Channels; D012433:Ryanodine; D013779:Tetrodotoxin; D014700:Verapamil; D002118:Calcium