Activity of cardiac L-type Ca2+ channels is sensitive to cytoplasmic calcium |
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Authors: | Christoph Romanin Jan -Olof Karlsson Hansgeorg Schindler |
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Affiliation: | (1) Institute for Biophysics, University of Linz, A-4040 Linz, Austria;(2) Institute of Neurobiology, Department of Histology, University of Göteborg, Sweden |
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Abstract: | Ca2+ -induced inactivation of L-type Ca2+ channels is proposed as an important negative feedback mechanism regulating Ca2+ entry. Here, for the first time, evidence for modification of heart L-type Ca2+ channel activity by cytoplasmic calcium is provided from excised insideout membrane patches. Ba2+ currents through cardiac L-type Ca2+ channels exhibited only modest inactivation in the absence of cytoplasmic Ca2+. Elevation of cytoplasmic Ca2+ to micromolar concentrations strikingly affected L-type Ca2+ channel activity as evaluated from ensemble average Ba2+ currents. Inactivation was markedly increased concomitant with a reduction of peak inward current, which was almost completely eliminated at about 15 M cytoplasmic Ca2+ concentration. Half maximal suppression of Ba2+ currents was observed at 2.3 M Ca2+. The observed modifications of L-type Ca2+ channel activity show that cytoplasmic Ca2+ induces channel closure. Below 4 M Ca2+, channels can be reversibly reactivated during repetitive depolarizations, while at high Ca2+ concentrations (15 M) most Ca2+ channels reside in a closed state. This may allow for a delicate regulation of Ca2+ entry, and consequently of heart contraction. |
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Keywords: | cardiac myocytes patch-clamp L-type Ca2+ channels Ca2+-induced inactivation |
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