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PMID: 7858131 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes.

Biophysical journal ·Vol. 67 ·No. 5 ·1994-11-00 ·Pages 1942-56

Cannell MB, Cheng H, Lederer WJ

Abstract

The intracellular calcium ([Ca2+]i) transient in adult rat heart cells was examined using the fluorescent calcium indicator fluo-3 and a laser scanning confocal microscope. We find that the electrically evoked [Ca2+]i transient does not rise at a uniform rate at all points within the cell during the [Ca2+]i transient. These spatial non-uniformities in [Ca2+]i are observed immediately upon depolarization and largely disappear by the time the peak of the [Ca2+]i transient occurs. Importantly, some of the spatial non-uniformity in [Ca2+]i varies randomly in location from beat to beat. Analysis of the spatial character of the non-uniformities suggests that they arise from the stochastic nature of the activation of SR calcium-release channels. The non-uniformities in [Ca2+]i are markedly enhanced by low concentrations of Cd2+, suggesting that activation of L-type calcium channels is the primary source of activator calcium for the calcium transient. In addition, the pattern of calcium release in these conditions was very similar to the spontaneous calcium sparks that are observed under resting conditions and which are due to spontaneous calcium release from the SR. The spatial non-uniformity in the evoked [Ca2+]i transient under normal conditions can be explained by the temporal and spatial summation of a large number of calcium sparks whose activation is a stochastic process. The results are discussed with respect to a stochastic local control model for excitation-contraction (E-C) coupling, and it is proposed that the fundamental unit of E-C coupling consists of one dihydropyridine receptor activating a small group of ryanodine receptors (possibly four) in a square packing model.

MeSH Terms
Animals Biophysical Phenomena Biophysics Cadmium/pharmacology Calcium/metabolism Calcium Channels/drug effects,metabolism Calcium Channels, L-Type In Vitro Techniques Intracellular Fluid/metabolism Kinetics Microscopy, Confocal Muscle Proteins/drug effects,metabolism Myocardial Contraction/physiology Myocardium/metabolism Rats Ryanodine Receptor Calcium Release Channel Sarcolemma/metabolism Sarcoplasmic Reticulum/metabolism
Chemicals
Calcium Channels Calcium Channels, L-Type Muscle Proteins Ryanodine Receptor Calcium Release Channel Cadmium Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cannell M B
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
Cheng H
Lederer W J
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(94)80677-0
Published
1994-11-00
Pages
1942-56
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1225569
Subset
IM
Grants
NHLBI NIH HHS · HL26975 · United States
NHLBI NIH HHS · HL36974 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(94)80677-0 PMC Full Text View journal details
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