F Gannier1, E White, J Y Le Guennec. 1. Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, CNRS EP 21, Faculté des Sciences, Tours, France.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Gentaro Iribe; Christopher W Ward; Patrizia Camelliti; Christian Bollensdorff; Fleur Mason; Rebecca A B Burton; Alan Garny; Mary K Morphew; Andreas Hoenger; W Jonathan Lederer; Peter Kohl Journal: Circ Res Date: 2009-02-05 Impact factor: 17.367