Excitation-contraction coupling in heart muscle.
We have investigated the links between electrical excitation and contraction in mammalian heart muscle. Using isolated single cells from adult rat ventricle, a whole-cell voltage-clamp technique and quantitative fluorescence microscopy, we have measured simultaneously calcium current (ICa) and [Ca2+]i (with fura-2). We find that the voltage-dependence of ICa and the [Ca2+]i-transient and the dependence of [Ca2+]i-transient on depolarization-duration cannot both be readily explained by a simple calcium-induced Ca-release ('CICR') mechanism. Additionally, we find that when [Ca2+]i and [Na+]i are at their diastolic levels, activation of the Na-Ca exchange mechanism by depolarization does not measurably trigger the release of Ca2+i. Finally, measuring ICa in adult and neonatal rat heart cells and using the alkaloid ryanodine, we have carried out complementary experiments. These experiments show that there may be an action of ryanodine on ICa that is independent of [Ca2+]i and independent of a direct action of the alkaloid on the calcium channel itself. Along with experiments of others showing that ryanodine binds to the sarcoplasmic reticulum calcium-release channel/spanning protein complex, our data suggests a model to explain our findings. The model links the calcium channels responsible for ICa to the sarcoplasmic reticulum by means of one or more of the spanning protein(s). Information from the calcium channel can be communitated to the sarcoplasmic reticulum by this route and, presumably, information can move in the opposite direction from the sarcoplasmic reticulum to the calcium channel.
Lederer
W J
WJ
University of Maryland School of Medicine, Dept. Physiology, Baltimore 21201.
Cannell
M B
MB
Cohen
N M
NM
Berlin
J R
JR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004558:Electric Stimulation; D005453:Fluorescence; D007474:Ion Exchange; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger
D015220:Calcium Channels; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D012964:Sodium; D002118:Calcium