Ca2+-movements in muscle modulated by the state of K+-channels in the sarcoplasmic reticulum membranes

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Abstract
A procedure has been developed to load Ca2+ reversibly by the sarcoplasmic reticulum (SR) of mechanically skinned muscle fibres from the toadBufo marinus under controlled conditions and was employed to investigate the effects of conditions known to reduce the K+ conductance located in the SR-membrane during Ca2+-loading on the amount of Ca2+ releasable by caffeine. 2. The amount of releasable Ca2+ was markedly increased compared to controls when 4-aminopyridine (4AP) (6 μM to 2 mM), tetraethylammonium (TEA), decamethonium (0.5 mM) or procaine (1 mM) were present in the Ca2+-loading solutions. All these substances are known to act as SR-K+-channel blockers. 3. The increased amount of releasable Ca2+ in the presence of the K+-channel blocker 4AP was observed both at low (0.3 mM) and at higher (1 mM) Mg2+ concentrations and was not affected by verapamil (20 μM), a known Ca2+-channel blocker of the sarcolemma nor by the Na+−K+ pump inhibitor, ouabain (1 mM). 4. In the presence of 0.1–5 μM ruthenium red, a known inhibitor of Ca2+ induced Ca2+ release from the SR, the amount of releasable Ca2+ was greatly increased by up to 300%. Addition of between 50 μM and 1.6 mM 4AP to ruthenium red Ca2+ loading solution modified differently the amount of releasable Ca2+, suggesting that the mechanism of action of 4AP is different from that of ruthenium red. 5. When all K+ ions in the loading solution were replaced by the less permeant Na+ ions the amount of releasable Ca2+ ions was also increased. 6. These results indicate that the amount of releasable Ca2+ from the SR is consistently modified under conditions aimed at interfering with the state of SR-K+-channels, suggesting that SR-K+-channels may play an important physiological role in the modulation of excitation-contraction coupling. One possible mechanism involving SR-K+-channels which could explain our results is discussed.