The effects of tetracaine (10-50 microM) and ryanodine (0.1-10 microM) were tested on the slow outward K+ current (Iso) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca2+ release from sarcoplasmic reticulum during contraction.
The effect of LCB29 was tested on twitch characteristics, tetanic tension, and K+ and voltage-clamp contractures of rat soleus muscle fibers. In concentrations ranging from 10(-6) to 5 x 10(-4) M, LCB29 simultaneously inhibited the twitch amplitude, the maximum rate of tension development, and the maximum rate of relaxation. In concentrations ranging from 10(-5) to 10(-4) M, tetanic tension (100 Hz, 1 s) was inhibited by the same amount. The effect of 5 x 10(-5) M LCB29 was studied on K+ contractures and contractures induced, under voltage-clamp conditions, by long-lasting depolarizations. Its effect was significantly stronger than those on twitch and tetanic tension. In addition, LCB29 had a dual effect on strength--duration curves for mechanical threshold. It increased both the rheobasic potential and the steepness of the curve. It is concluded that LCB29 exerts a direct myorelaxant effect on rat soleus muscle; two sites of action are probably involved.
The effects of caffeine, ryanodine, and rapid cooling were tested on the depolarization-induced contraction and the apamin-insensitive slow outward current (Iso) of voltage-clamped (double mannitol gap) single frog muscle fibers. Subthreshold caffeine concentrations (0.5-2 mM) induced a monotonic increase in contractile and Iso amplitude. Whatever the concentration, the increase in contraction was roughly twice the one in current. Similar results were obtained upon rapid cooling (20-4 degrees C) in the presence of 0.5 mM caffeine. In the absence of external Na+ (choline-substituted) 10(-5) M ryanodine induced a delayed increase (approximately 30 min) in contraction and in current, shortly before the development of a drastic and irreversible contracture. Here again, the increase in contraction was twice that in current. In the presence of 5 mM tetraethylammonium (TEA) and (or) 25 nM charybdotoxin, 2 mM caffeine still induced a strong facilitating effect on contraction but the parallel increase in current was strongly reduced. The linear relationship between the increase in current and contractile amplitude has a slope approximately 0.5 (whatever the drug used to increase contractility); it is approximately 0.1 in the presence of TEA and (or) charybdotoxin. In conclusion, provided the changes in contractile amplitude are caused by parallel changes in depolarization-induced sarcoplasmic reticulum Ca2+ release, about 50% of the apamin-insensitive Iso is controlled by internal Ca2+ release. The main part of this current corresponds to the TEA- and charybdotoxin-sensitive component of Iso.
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