Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus.
Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels, and it is suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009130:Muscle, Smooth / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D012530:Saxitoxin / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D014599:Uterus / Q000502:physiology*
D015220:Calcium Channels; D007473:Ion Channels; D015222:Sodium Channels; D012530:Saxitoxin; D010121:Oxytocin; D008274:Magnesium; D009543:Nifedipine; D000241:Adenosine; D007545:Isoproterenol