Ryanodine receptors voltage-dependent coupling

Calcium couples muscle membrane excitation to filament contraction. Important work has focused on the proteins present in the T-tubule/SR junction. One protein, an integral component of the T-tubular membrane, is a form of L-type, dihydropyridine-sensitive, voltage-dependent calcium channel. Another, the ryanodine receptor (RyR), is a large protein associated with the SR membrane in the triad that may couple the conformational changes in the Ca2+ channel protein induced by T-tubular depolarization to the Ca2+ release from the SR (Fig. 43-6). 

The first molecule, the Ca2+ channel, is required for coupling at the triad. Skeletal muscle contains higher concentrations of this L-type Ca2+ channel that can be accounted for on the basis of measured voltage-dependent Ca2+ influx because much of the Ca2+ channel protein in the T-tubular membrane does not actively gate calcium ion movement but, rather, acts as a voltage transducer that links depolarization of the T-tubular membrane to Ca2+ release through a receptor protein in the SR membrane. The ryanodine receptor mediates sarcoplasmic reticulum Ca2+ release. The bar-like structures that connect the terminal elements of the SR with the T-tubular membrane in the triad are formed by a large protein that is the principal pathway for Ca2+ release from the SR. This protein, which binds the... 

A special coupling between extracellular Ca influx and the ryanodin receptor exists in muscle cells. There, a voltage-dependent Ca channel, the dihydropyridine receptor, is coupled directly to the cytoplasmic domain of the ryanodin receptor (see Fig. 6.7a). A depolarization of the cell membrane is transmitted in this system via an electromechanical coupling directly to the gating state of the ryanodin receptor. 

While skeletal muscle ryanodine receptors are involved in excitation — contraction coupling through direct interactions with voltage-gated Ca2+ channels, in other cell types ryanodine receptor Ca2+ channels located on the ER membrane are opened by cADPR in a Ca2+-CaM-dependent fashion. Ca2+ and plant metabolites such as the diterpenoid alkaloid ryanodine and the methylxanthine caffeine promote opening of the ryanodine receptor Ca2+ channel. Ryanodine can also negatively modulate the receptor (Table 4.4). 

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