Modulation of Calcium Channels of Twitch Skeletal Muscle Fibres of the Frog by Adrenaline and Cyclic Adenosine Monophosphate

1. Modulation of fast and slow Ca2+ channels of frog skeletal muscle by adrenaline (10(-6) to 10(-5) M) and cyclic AMP was investigated using intracellular voltage recordings in intact fibres and a voltage-clamp technique in cut fibres. 2. In tetraethylammonium (TEA), Cl(-)-free Ringer solution, adrenaline increased the maximum rate of rise of Ca2+ spikes by 85% and in a similar solution, peak slow Ca2+ current (ICa,s) by 51%. 3. Application of cyclic AMP to the cut ends of fibres, produced a relative increase of ICa,s of ca. 24%. The effect was maintained for ca. 2 h. 4. Changes in the time course of ICa,s were produced by adrenaline and cyclic AMP: the limiting values of time-to-peak current measured as a function of membrane potential were lower (ca. 41% in adrenaline and ca. 34% in cyclic AMP) than those found in control experiments. Also, ICa,s decayed faster in the presence of adrenaline or cyclic AMP. These changes can be explained by exhaustion of Ca2+ in the lumen of transverse tubular system and do not require the assumption of kinetic variations. 5. Fast Ca2+ currents (ICa,f) which could not be blocked by nifedipine were also recorded. Cyclic AMP greatly increased the amplitude of ICa,f but had no obvious effects on ICa,f kinetics. 6. Application of catalytic subunit of cyclic AMP-dependent protein kinase by diffusion or by pressure injection also increased the amplitude of ICa,s and ICa,f. Pressure injection brought about modifications in the time course of ICa,s that cannot be explained by depletion of Ca2+. 7. Mechanical experiments were performed on single fibres. Nominally Ca2+-free solutions prevented the development and the maintenance of positive inotropic effect of adrenaline on twitch tension. Development of twitch potentiation was dependent upon the frequency of stimulation. Adrenaline was practically ineffective if no stimulation was applied. 8. It is concluded that both populations of Ca2+ channels are modulated by adrenergic stimulation probably via cyclic AMP, and that twitch potentiation may be mediated by a Ca2+ entry through Ca2+ channels.