Activity of glibenclamide-sensitive K+ channels under unstimulated conditions in smooth muscle cells of pig proximal urethra

Abstract

The membrane potential in pig proximal urethra was examined by use of the microelectrode technique. In cells 1-2 cm from the bladder neck the membrane potential was quiescent, with a value of -37.2+/-2.5 mV (n = 16). In some cells small spontaneous de- and hyperpolarizations were seen. Glibenclamide (1 microM) caused a small but significant depolarization in tissue strips (12+/-3 mV, n = 3) and also in dispersed cells using whole-cell patch electrodes (13+/-3 mV, n = 5). In the conventional whole-cell voltage-clamp configuration, glibenclamide reduced the noise level of the basal membrane current at -50 mV and inhibited the membrane current in symmetrical 140 mM K+ conditions. In cell-attached patches, brief openings of a glibenclamide-sensitive 43 pS K+ channel (K(GS)-43 pS) were seen even under unstimulated conditions and greater activation occurred in the same membrane patch on subsequent application of 100 microM levcromakalim. These results provide direct evidence that glibenclamide-sensitive K+ channels may play a role in maintaining the resting membrane potential of pig proximal urethra under unstimulated conditions.

Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

“…Our results suggest that this is not the case in rat mesenteric small arteries at high concentrations of nicorandil, since K + current activation by 300 mM nicorandil was una ected by inhibition of GC with LY 83583 (Figure 3). Similarly, in pig urethra, Teramoto & Brading (1997) found that methylene blue did not a ect channel activation by nicorandil. Relaxations to nicorandil at concentrations below 300 mM, however, were almost completely inhibited by a high concentration of LY 83583 (10 mM, Figure 7a).…”

“…In rabbit portal vein, the channel activated may have a slightly lower conductance of 26 pS (Kamouchi & Kitamura, 1994), though a higher conductance channel has also been reported to be activated by another K ATP channel opener, pinacidil, in this tissue (50 pS, Kajioka et al, 1991). In cells from pig urethra, Teramoto & Brading (1997) found that nicorandil activated a glibenclamide-sensitive channel with a somewhat larger conductance, 43 pS in symmetrical high [K + ]. The channels activated by nicorandil and other K ATP channel openers have often been found to also be susceptible to activation by intracellular nucleoside diphosphates (Kamouchi & Kitamura, 1994;Teramoto & Brading, 1997).…”

“…In cells from pig urethra, Teramoto & Brading (1997) found that nicorandil activated a glibenclamide-sensitive channel with a somewhat larger conductance, 43 pS in symmetrical high [K + ]. The channels activated by nicorandil and other K ATP channel openers have often been found to also be susceptible to activation by intracellular nucleoside diphosphates (Kamouchi & Kitamura, 1994;Teramoto & Brading, 1997). In rat mesenteric arterial cells, Zhang & Bolton (1995) found that pinacidil or intracellular GDP activated a glibenclamide-sensitive channel with a conductance of 20 pS in 60 mM…”

“…In both portal vein and coronary artery cells, nicorandil has been reported to activate channels that are inhibited by intracellular ATP (K ATP channels); in rat portal vein cells the channel activated by nicorandil has been reported to also be activated by intracellular Ca 2+ (Kajioka et al, 1990), while in rabbit portal vein cells the channel is activated by intracellular nucleoside diphosphates as well as inhibited by ATP (Kamouchi & Kitamura, 1994). The sensitivity of nicorandil-activated currents in vascular smooth muscle to the sulphonylurea glibenclamide, which appears to be selective for K ATP channels in this tissue at concentrations up to 10 mM has not been investigated, though glibenclamide inhibition of nicorandilactivated currents has been reported in cells from the pig proximal urethra (Teramoto & Brading, 1997). The K ATP channel opening action of nicorandil, in common with other K ATP channel openers, is usually thought to occur as a direct action on the channel (see Quayle et al, 1997 for review).…”

Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra

“…This might provide useful information for the synthesis of novel types of K þ channel opener and mefenamic acid may serve as a useful prototype for designing more selective compounds for K ATP channels as well as BK Ca channel openers. Since these channels can be activated under normal physiological conditions around the resting membrane potential (Teramoto et al, 1997), they represent a significant target for the treatment of various urinary tract dysfunctions such as urge incontinence in urinary bladder and bladder outflow obstruction in urethra.…”