Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium

Dec 9, 2009Cell calcium

Location, activity, and roles of calcium-activated potassium channels in rat uterine muscle

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Abstract

All three small conductance potassium channel isoforms (SK1-3) are consistently expressed in rat myometrium throughout pregnancy.

SK1-3 channels are involved in regulating outward current and membrane potential in the myometrium.
Inhibition of SK channels led to increased cytosolic calcium levels and force in myometrial strips.
The functional impact of SK channel inhibition was greater than that of large conductance channels (BK).
SK channel activity is associated with maintaining quiescence in the pregnant myometrium.

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Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels.

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Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium

Abstract

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