Regulation of cardiac muscle contraction by intracellular Ca2+.
In this short review, some of the factors which influence the intracellular Ca2+ transients and contraction in mammalian cardiac muscles which we have been examining are discussed. The processes concerning the change in [Ca2+]i and contraction are divided into three steps following the scheme proposed by Blinks [6]: Upstream, Central, and Downstream. However, these processes are interrelated. Although the Ca2+ transient is an important step for triggering contraction, it is influenced by the following Central and Downstream mechanisms. The evaluation of Ca2+ sensitivity of the contractile elements (Central mechanism) in intact preparations is discussed; measurement of the relation between [Ca2+]i and tension in tetanic contraction is one of the possible methods. A change in the Ca2+ binding to troponin-C is an important factor to determine the Ca2+ sensitivity but other mechanisms are also considered to be involved. In cardiac muscles, the feedback mechanism from the Downstream, in particular the cross-bridge attachment and detachment, to the Central processes is a physiologically important mechanism in the determination of contractile properties. This feedback mechanism alternatively influences the intracellular Ca2+ transient by changing the affinity of troponin-C for Ca2+. Thus, the interpretation of the measured Ca2+ transients is not simple and the numerous factors involved must be considered. Further study is necessary to elucidate the molecular mechanisms which are responsible for the feedback from the Downstream mechanism to the Central and Upstream mechanisms.