SUMMARY1. Ca channel currents were recorded in Cs-loaded myometrial strips from pregnant rats after addition of tetraethylammonium chloride and 4-aminopyridine (10 mM each) by means of a double sucrose-gap technique.2. During a depolarizing pulse, the decay of Ca channel current was slowed down when external Ca was replaced by Ba or Sr. This decay represented an inactivation phenomenon, as assessed by the decreased amplitude of inward tail currents following progressively longer depolarizations, the absence of shift in peak conductance curves against membrane potential, and the stable value of the reversal potential when Ba current was increased during conditioning pulses.3. Inactivation of Ca and Ba currents through Ca channels was studied using the double-pulse method. Conditioning pulses that produced maximal Ca current induced maximal inactivation; with stronger depolarizations, inactivation decreased but was not completely prevented at the expected Ca reversal potential. Increasing the amount of Ca entering the cell during the pre-pulse reduced both amplitude and kinetics of test Ca currents. These results were not observed with Ba as charge carrier suggesting the participation of different mechanisms in inactivation.4. With Ca as charge carrier, increasing the external Ca speeded the rate of inactivation. This was not observed with Ba outside. Addition of Co (2-5 mM) reduced the amplitude of both Ca and Ba currents but slowed the inactivation of only the Ca current.5. Recovery from inactivation was described as a two-exponential process only when the conditioning pulse elicited a Ca inward current. In all other cases, recovery from inactivation was represented as a single exponential curve.6. It is suggested that inactivation of Ca channels in rat uterine smooth muscle is mediated by both internal Ca-dependent and potential-dependent mechanisms.
SUMMARY1. Action potentials and membrane currents were recorded by means of a double sucrose-gap technique from Cs-loaded strips from pregnant rats superfused in Ca-free EGTA-containing solutions.2. When external Ca was reduced below 1 ,lM in the presence of 1 mM-EGTA, step depolarizations from a holding potential close to the normal resting potential produced tetrodotoxin-resistant inward currents. These currents were suppressed after removal of external Na and blocked by a variety of Ca-channel blockers such as Mn, Co, Ni and nifedipine.3. Inactivation of the inward Na current was studied using a double-pulse protocol. The degree of inactivation of the Na current was almost maximal for depolarizations of + 50 mV. Application of stronger depplarizations did not significantly increase it and had no effect on recovery from inactivation. Similarly, increasing the duration of the conditioning pulse from 30 to 250 ms had no further effect on both amplitude and kinetics of the Na current. These results suggest that the Na current inactivation reflects a pure voltage-dependent mechanism.4. The effects of external Ca were studied over a 109-fold range in concentration. When external Ca was gradually increased from 1 nm to 1 ,IM, the inward Na current was reduced and finally abolished. As the external Ca was increased over 0-5 mM, inward current reappeared and increased as Ca became the charge carrier.5. When Na was the charge carrier, external Ca was the most effective divalent cation in blocking the Ca channel with a half-blockage concentration of 0.1 /,M.Addition of millimolar concentrations of Ca and Sr also reduced the Ba current while adding Ba to Ca-containing solution produced no increase in current. 6. Membrane currents in solutions containing both Ba and Ca ions were less than in solutions containing either Ca or Ba at the same concentration, suggesting that Ca channels are single-file multi-ion pores.7. We conclude that the selectivity of uterine Ca channels depends on the presence of external Ca. In the absence of Ca, these channels become permeable to other divalent (Ba and Sr) and monovalent (Na) cations.
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