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. Whole-cell voltage clamp was done on 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. 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 (or Ba2+), 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. We conclude that 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, 0.56 on day 14, 0.90 on day 18, and 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. 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 we suggest that the fast Na+ current may be involved in spread of excitation. 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) (but not IBa) 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 cannot be explained by a stimulation of ICa(s).
Sperelakis
N
N
Department of Physiology & Biophysics, University of Cincinnati College of Medicine, OH 45267-0576.
Inoue
Y
Y
Ohya
Y
Y
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D009130:Muscle, Smooth / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D012530:Saxitoxin / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D015149:Tocolytic Agents / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism*
D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels; D015149:Tocolytic Agents; D012530:Saxitoxin