Regulation of calcium release channel in sarcoplasmic reticulum.

Abstract

In this review, we summarized the results obtained mainly by flux measurements through Ca2+ channel in HSR vesicles. The Ca2+ channel has a large pore which passes not only divalent cations such as Ca2+, Mg2+, and Ba2+ and monovalent cations such as Na+, K+, and Cs+, but also large ions such as choline and tris. The permeation rates of choline and glucose through the Ca2+ channel were measured quantitatively by the light scattering method. The slow permeation of such molecules may reflect the structure of pores since the permeation process is the rate-limiting step for such large molecules. Neutral molecules such as glucose became permeable in the presence of submolar KCl, which suggests that pore size of the channel becomes larger in KCl. The apparent permeation rates of Ca2+ and Mg2+ obtained from the flux measurement were the same, although their single-channel conductances were different. This discrepancy was explained by the fact that flux measurements reflects the open rate of the channel. Thus, complementarity between the flux measurement and single-channel recording was demonstrated. From the effects of K+ on the action of regulators on Ca2+ channel, it was suggested that the Ca2+ channel has many binding sites for activators and inhibitors. There are two kinds of Ca2+ binding sites for activation and inhibition. Activation sites for Ca2+, caffeine, and ATP are different and inhibition sites for Ca2+ and procaine are different. The binding sites for ruthenium red and Mg2+ are the same as the activation and/or inhibition sites for Ca2+. Ryanodine-treated Ca2+ channel became permeable to glucose even in the absence of KCl. The conformational state of the channel opened by ryanodine is different from that opened by Ca2+, caffeine, and ATP. The maximal flux rates of choline and glucose induced by ryanodine were smaller than those attained by caffeine and ATP. This result is consistent with the observation obtained by single-channel recording; the maximal value of single-channel conductance after ryanodine treatment becomes 40-50% of the value before the treatment. It is likely that the radius of the pore opened by ryanodine is smaller than that opened by Ca2+, caffeine, or ATP. The flexibility of the channel may be decreased in the open locked state induced by ryanodine. The Ca2+ response to open the channel by micromolar Ca2+ was lost when calsequestrin was released from the vesicles. It is possible that calsequestrin acts as an endogenous regulator of Ca2+ channel through triadin in excitation-contraction coupling.