The effects of calcium channel modulators on contractions of tonic frog muscle fibres.

Effects of adrenaline (ADR) and the dihydropyridine Ca channel agonist CGP-IOS were studied on twitch and tetanic contractions of isolated tonic muscle fibres or small muscle fibre bundles containing tonic fibres of the frog Rana temporaria. Tetanization caused a gradual increase of tension between 10 and 70 Hz. CGP-IOS produced an increase in twitch amplitude. After CGP-IOS administration (2 x 10(-6) - 10(-5) mmol/l), the twitch amplitude increased and the high frequency tetanus developed more rapidly. However, during the phase of high tension level a breakdown of tetanic tension appeared and this occurred earlier at higher stimulation frequencies. After the end of tetanization the contraction curve did not return to the initial level, so that the remaining contraction (contracture) lasted 2 to 5 min. Sometimes just after replacement of CGP-IOS by Ringer, a large enhancement of tetanus amplitude was observed followed by long lasting contractures. ADR (10(-5) mmol/l) increased the tetanic tension without changing the shape of tetanus but did not affect twitch amplitude. Adrenergic modulation of tension requires extracellular Ca2+. Combined administration of ADR and CGP-IOS had an integrative effect, so that independent action of each of them can be assumed. It is to suggest that direct and indirect Ca channel modulators, DHP derivatives and ADR, have different targets. The sites responsible for adrenergic modulation of the contraction may be Ca channels not identical to DHP-sensitive channels, i.e. Ca-releasing channels in SR or the DHP-insensitive Ca channels in muscle membrane.