The biochemistry of uncontrolled calcium entry

1 December 1983

journal article
research article
Published by Oxford University Press (OUP) in European Heart Journal

Vol. 4 (suppl H) , 29-41
https://doi.org/10.1093/eurheartj/4.suppl_h.29

Abstract

The Ca²⁺ paradox is characterized by a rapid and uncontrolled entry of ca²⁺ Whilst the consequence of the resultant gain in Ca²⁺ are relatively well defined, uncertainty exists concerning the route of entry. Possible routes include passive diffusion across damaged sarcolemma and intercalated discs, active transport in exchange for K⁺ or Na⁺ and entry through the voltage-activated, Ca²⁺ slow channels. The following experiments were designed to differentiate between these possibilities. Isolated spontaneously beating Sprague-Dawley rat hearts were perfused at 37ΰC with Ca²⁺ perfusion buffer for >1 min before starting Ca²⁺ repletion. Adding 2–4 m mol l⁻¹ Co²⁺ or Mn²⁺ before, during but not coincident with Ca²⁺ repletion protected against the paradox as indicated by an absence of myoglobin release and Ca²⁺ overload. Despite this protection marked distortion of the glycocalyx occurred, with splitting of the basement coat and blebbing. The intercalated discs, however, remained intact. It seems unlikely therefore that splitting of the basement coat necessarily results in an uncontrolled entry of Ca²⁺ Since Mn²⁺ and Co²⁺ block Ca²⁺ entry through the slow channels their failure to prevent the uncontrolled entry of Ca²⁺ when added at the time of Ca²⁺ repletion favours the view that Ca²⁺ entry during the paradox does not depend upon entry of Ca²⁺ through the slow channels. In other experiments hearts were preloaded with Na²⁺ to alter intracellular Na²⁺ before Ca²⁺ repletion. This procedure did not markedly affect the gain in Ca²⁺ These findings will be discussed in terms of the route(s) and consequence(s) of the uncontrolled entry of Ca²⁺ that occurs when Ca²⁺ is reintroduced after a period of Ca²⁺-free perfusion.

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