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Article

S.Y. Wang, M. Yoshino, J.L. Sui, M. Wakui, P.N. Kao, and C.Y. Kao

From the Department of Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203

In freshly dissociated uterine myocytes, the outward current is carried by K⁺ through channels highly selective for K⁺. Typically, nonpregnant myocytes have rather noisy K⁺ currents; half of them also have a fast-inactivating transient outward current (I_TO). In contrast, the current records are not noisy in late pregnant myocytes, and I_TO densities are low. The whole-cell I_K of nonpregnant myocytes respond strongly to changes in [Ca²⁺]_o or changes in [Ca²⁺]_i caused by photolysis of caged Ca²⁺ compounds, nitr 5 or DM-nitrophene, but that of late-pregnant myocytes respond weakly or not at all. The Ca²⁺ insensitivity of the latter is present before any exposure to dissociating enzymes. By holding at –80, –40, or 0 mV and digital subtractions, the whole-cell I_K of each type of myocyte can be separated into one noninactivating and two inactivating components with half-inactivation at approximately –61 and –22 mV. The noninactivating components, which consist mainly of iberiotoxin-susceptible large-conductance Ca²⁺-activated K⁺ currents, are half-activated at 39 mV in nonpregnant myocytes, but at 63 mV in late-pregnant myocytes. In detached membrane patches from the latter, identified 139 pS, Ca²⁺-sensitive K⁺ channels also have a half-open probability at 68 mV, and are less sensitive to Ca²⁺ than similar channels in taenia coli myocytes. Ca²⁺-activated K⁺ currents, susceptible to tetraethylammonium, charybdotoxin, and iberiotoxin contribute 30–35% of the total I_K in nonpregnant myocytes, but <20% in late-pregnant myocytes. Dendrotoxin-susceptible, small-conductance delayed rectifier currents are not seen in nonpregnant myocytes, but contribute 20% of total I_K in late-pregnant myocytes. Thus, in late-pregnancy, myometrial excitability is increased by changes in K⁺ currents that include a suppression of the I_TO, a redistribution of I_K expression from large-conductance Ca²⁺-activated channels to smaller-conductance delayed rectifier channels, a lowered Ca²⁺ sensitivity, and a positive shift of the activation of some large-conductance Ca²⁺-activated channels.

Key Words: smooth muscle cells • uterine myocytes • K⁺ channels • pregnancy • ovarian hormones

Dr. C.Y. Kao died on May 26, 1998.

Address correspondence to Peter N. Kao, M.D., Ph.D., Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA 94305-5236. Fax: 650-725-5489; E-mail: peterkao{at}leland.stanford.edu

Abbreviations: 4-AP, 4-aminopyridine; ChTX, charybdotoxin; DTX, -dendrotoxin; HP, holding potential; i-V, current– voltage; IbTX, iberiotoxin; I_TO, transient outward current; MCDP, mast-cell degranulating peptide; TEA, tetraethylammonium; V-g, voltage–conductance; V-h, voltage–steady state inactivation

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