Ryanodine receptors conformational changes

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). 

Figure 6.6. Excitation contraction coupling in skeletal muscle (a, b) and heart muscle (c). In skeletal muscle, the anesthetics receptor (DHPR) and the ryanodine receptor (RyR) are in direct contact (a). The conformational change to the former that occurs in response to membrane depolarization is sufficient to induce Ca release from the SR a flow of Ca across the plasma membrane is not necessary (b). In heart muscle, however, this direct link does not exist, and Ca must therefore enter through the DHPR first (c).

Fig. 6.8 Tetrameric Ca2+ channels and control of Ca2+ release, a) A change in the membrane potential (V) induces a conformational change in the dihydropyridine receptor of skeletal muscle this is transmitted as a signal to the structurally coupled ryanodin receptor. Opening of the Ca2+ channel takes place and efflux of Ca2+ from the sarcoplasmic reticulum into the cytosol occurs, b) In cardiac muscle, the release of Ca2+takes place by a Ca2+-induced mechanism. A potential change V induces...

Fig. 47.3. Events leading to sarcoplasmic reticulum calcium release in skeletal muscle. 1. Acetylcholine, released at the synaptic cleft, binds to acetylcholine receptors on the sar-colemma, leading to a change of conformation of the receptors such that they now act as an ion pore. This allows sodium to enter the cell and potassium to leave. 2. The membrane polarization that results from these ion movements is transmitted throughout the muscle fiber by the T-tubule system. 3. A receptor in the T-tubules (the dihydropyridine receptor, DHPR) is activated by membrane polarization (a voltage-gated activation) such that activated DHPR physically binds to and activates the ryanodine receptor in the sarcoplasmic reticulum (depolarization-induced calcium release). 4. The activation of the ryanodine receptor, which is a calcium channel, leads to calcium release from the SR into the sarcoplasm. In cardiac muscle, activation of DHPR leads to calcium release from the T-tubules, and this small calcium release is responsible for the activation of the cardiac ryanodine receptor (calcium-induced calcium release) to release large amounts of calcium into the sarcoplasm.

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