Inactivation of calcium channel current in rat uterine smooth muscle: evidence for calcium‐ and voltage‐mediated mechanisms.

Abstract

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.

(+)−[3H]‐PN 200–110 binding to cell membranes and intact strips of portal vein smooth muscle: characterization and modulation by membrane potential and divalent cations

“…Thus, the affinity of (+)-[3H]-PN 200-110 binding was increased by both membrane depolarization and addition of external calcium. These observations can be correlated to electrophysiological studies demonstrating that inactivation of calcium channels in smooth muscles is mediated by both calciumdependent and membrane potential-dependent mechanisms (Jmari et al, 1986b;Ohya et al, 1988). …”

Potential‐dependent inward currents in single isolated smooth muscle cells of the rat ileum.

“…HVA Ca2+ current HVA Caa2+ channels have been found in all SMCs studied previously (Kldckner & Isenberg, 1985;Ganitkevich, Shuba & Smirnov, 1986Caffrey et al 1986;Jmari et al 1986;Ohya et al 1986;Ame'dee et al 1987;Benham et al 1987;Aaronson 566 Ca2+ AND Nat CHANNELS IN SMOOTH MUSCLE et al 1988;Loirand et al 1989;Yamamoto et al 1989;Hisada, Kurachi & Sugimoto, 1990;Aaronson & Russell, 1991). They possess the following main features: (1) an apparent activation threshold usually in the voltage range between -40 and -20 mV in the presence of a physiological Ca2+ concentration; (2) dependence of the inactivation process both on Ca2+ ions and the membrane potential; (3) larger wholecell current and unitary conductances in the presence of Ba2+ rather than Ca2+ as a current carrier; and (4) high sensitivity to dihydropyridine antagonists.…”

Ca2+ currents in single myocytes from human mesenteric arteries: evidence for a physiological role of L‐type channels.

“…Dependence of inactivation of L-type Ca2+ channels on Ca2+ entry into cells was described in a variety of tissues (see Eckert & Chad, 1984), including visceral and vascular SMCs (Jmari, Mironneau & Mironneau, 1986Ganitkevich, Shuba & Smirnov, 1986, 1991Ohya, Terada, Kitamura & Kuriyama, 1986;Ohya, Kitamura & Kuriyama, 1988;Matsuda et al 1990) and is considered to be a fundamental property of L-type Ca2+ channels. Indications of a Ca2+-dependent inactivation of Ca2+ channels are a U-shaped potential dependence of availability of ICa measured in a two-pulse protocol and a sensitivity of this process to the type of divalent cation entering through Ca2+ channels.…”