Different Ca super(2+) releasing action of caffeine and depolarisation in skeletal muscle fibres of the rat

• Published in: The Journal of physiology 2001-03, Vol.531 (3), p.715-728
• Main Authors: Lamb, G D, Cellini, MA, Stephenson, D G
• Format: Article
• Language: English
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2001.0715h.x

* 1 The relative abilities of caffeine and transverse tubular (T-) system depolarisation to induce Ca super(2+) release in mammalian skeletal muscle were compared in mechanically skinned fibres of the rat, in order to determine whether normal excitation-contraction (E-C) coupling is achieved by up-regulating the Ca super(2+)-induced Ca super(2+) release process, as caffeine is known to do. * 2 Caffeine triggered Ca super(2+) release in soleus (slow-twitch) fibres at much lower concentrations than in extensor digitorum longus (EDL) (fast-twitch) fibres when the sarcoplasmic reticulum (SR) of each type was loaded with Ca super(2+) at close to endogenous levels. The difference in caffeine sensitivity resulted at least in part from the SR being loaded endogenously at near maximal capacity in soleus fibres but at less than half of maximal capacity in EDL fibres. The caffeine sensitivity could be reversed by reversing the relative level of SR loading. * 3 The ability of caffeine to induce Ca super(2+) release was markedly reduced by lowering the level of SR loading or by raising the free [Mg super(2+)] from 1 to 3 mm. Caffeine, even at 30 mm, triggered little or no Ca super(2+) release in EDL fibres (a) at 1 mm (physiological) Mg super(2+) when the SR was loaded at two-thirds or less of the endogenous level, and (b) at 3 mm Mg super(2+) when the SR was loaded at close to the endogenous level. In contrast, depolarisation potently elicited Ca super(2+) release under these conditions in the same fibres. * 4 The inability of 30 mm caffeine to induce Ca super(2+) release under certain conditions was not attributable to desensitisation or inactivation of the release channels, because there was no response even upon initial exposure to caffeine and depolarisation always remained able to trigger Ca super(2+) release. It instead appeared that caffeine was a relatively ineffectual stimulus in EDL fibres except under conditions where (a) the SR was heavily loaded, (b) the free [Mg super(2+)] was low, or (c) a high [Cl super(-)] was present. * 5 These results show that the normal E-C coupling mechanism in mammalian skeletal muscle does not involve just enhancing Ca super(2+)-induced Ca super(2+) release, and evidently requires the removal or bypassing of the inhibitory effect of Mg super(2+) on the Ca super(2+) release channels.