Selectivity of calcium channels in rat uterine smooth muscle: interactions between sodium, calcium and barium ions.

Abstract

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.

Ionic channels in smooth muscle studied with patch-clamp methods.

“…It seems that Ca ion controls ionic selectivity of Ca channel and that Na ions can pass the Ca channel under Ca-deficient condition. Similar results have been obtained with the sucrose-gap method in the muscle strips of guinea-pig taenia caeci [12], cat and guinea-pig small intestine [51], and rat myometrium [30].…”

Tetrodotoxin‐Sensitive Sodium Current in Sheep Lymphatic Smooth Muscle

“…The sodium current described in the present study should not be confused with the non-specific currents carried by sodium ions through Ca2+ channels in low calcium solutions both in heart (Garnier, Rougier, Gargouil & Coraboeuf, 1969) and in smooth muscle (Jmari, Mironneau & Mironneau, 1987). The currents described by Garnier et al (1969) and Jmari et al (1987) were slow to inactivate (inactivation took more than 200 ms), insensitive to TTX and blocked by Ni2+ and nifedipine.…”

“…The currents described by Garnier et al (1969) and Jmari et al (1987) were slow to inactivate (inactivation took more than 200 ms), insensitive to TTX and blocked by Ni2+ and nifedipine. Rather the properties of the sodium current detailed in the present study, namely fast inactivation kinetics (r < 20 ms), high sensitivity to TTX (Kd < 20 nM) and insensitivity to Ni2+ and nifedipine, are more like the INa found in nerve and skeletal muscle.…”

Properties of calcium channels in guinea‐pig gastric myocytes.

“…Figure 8B compares the time course of inactivation of Ca2+ channel when Ca2+ and Ba2+ are the charge carriers through the channel in a cell dialysed with EGTA. As shown previously, when Ca2+ was the charge carrier, a fast (,r) and a slow (Ts) time constant could well describe the inactivation kinetics of ICa When Ba2+ was substituted for Ca2+, one time constant was almost sufficient to describe the inactivation of the calcium channel similar to rabbit ileal cells (Ohya et al 1986 (Bulbring & Tomita, 1970;Jmari, Mironneau & Mironneau, 1987). Figure 9 shows that Na+ current through the Ca2+ channel was slightly larger in amplitude than ICa Jmari et al 1987) and the voltage dependence of its activation was (0) shifted by 10-20 mV to more negative potentials (Ohya et al 1986;Jmari et al 1987 (Fig.…”