Activity of cardiac L-type Ca2+ channels is sensitive to cytoplasmic calcium.
Ca(2+)-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 inside-out 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 microM cytoplasmic Ca2+ concentration. Half maximal suppression of Ba2+ currents was observed at 2.3 microM Ca2+. The observed modifications of L-type Ca2+ channel activity show that cytoplasmic Ca2+ induces channel closure. Below 4 microM Ca2+, channels can be reversibly reactivated during repetitive depolarizations, while at high Ca2+ concentrations (approximately 15 microM) most Ca2+ channels reside in a closed state. This may allow for a delicate regulation of Ca2+ entry, and consequently of heart contraction.
Romanin
C
C
Institute for Biophysics, University of Linz, Austria.
Karlsson
J O
JO
Schindler
H
H
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*
D015220:Calcium Channels; D001464:Barium; D002118:Calcium