Potassium Currents in Freshly Dissociated Uterine Myocytes from Nonpregnant and Late-Pregnant Rats

Abstract

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 (ITO). In contrast, the current records are not noisy in late pregnant myocytes, and ITO densities are low. The whole-cell IK 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 IK 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 IK 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 IK in late-pregnant myocytes. Thus, in late-pregnancy, myometrial excitability is increased by changes in K+ currents that include a suppression of the ITO, a redistribution of IK 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.

Remodeling of Kv4.3 Potassium Channel Gene Expression under the Control of Sex Hormones

“…The Kv4.3 down-regulation at the end of pregnancy agrees with the reported down-regulation of Ito currents in late pregnant myometrium (23) and with the recent findings that the expression levels of MaxiK channel protein and corresponding mRNA levels dramatically diminish near the end of gestation (32). Because MaxiK channel activity regulates myometrium contractility (34), the lower levels of MaxiK channel protein may facilitate a higher contractile activity.…”

A-type potassium currents in smooth muscle

“…As with pregnant rats (e.g., Ref. 119), ovariectomized rats treated with 17␤-estradiol had drastically diminished A-type currents. Taken together, these data suggest that estrogen is a negative regulator of A-type channel expression in the rat myometrium.…”

“…In most species, including humans, plasma levels of 17␤-estradiol and progesterone increase during pregnancy (110). These changes are associated with a decline in A-type current densities in myometrial smooth muscle cells during the transition from a nonpregnant to a late-pregnant state (119). The changes in myometrial A-type currents have been mimicked by administration of 17␤-estradiol to immature female rats.…”

Potassium channels and uterine function

“…In rat non-pregnant myocytes, BKCa channels contribute approximately 35% to whole cell repolarizing K + current; however by late gestation, electrophysiological measurements show that loss of BKCa-generated currents is concomitant with an increased contribution of other K + channel types to maintain uterine quiescence [1]. Contractile studies in mid-and late pregnant rats show that the BKCa opener NS1619 and inhibitor iberiotoxin (IbTX) do not alter spontaneous contractile activity induced by prostaglandins [2].…”