Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP‐sensitive K⁺ channels

Abstract

1 We have investigated the possible roles of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP-sensitive K + channels (K ATP channels) by use of patch-clamp and reverse transcriptase -polymerase chain reaction (RT -PCR) techniques. 2 In voltage-clamp experiments, not only diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2 activator, caused an inward current at a holding potential of À50 mV in symmetrical 140 mM K + conditions. 3 Gliclazide (p1 mM), a selective SUR1 blocker, inhibited the 10 mM pinacidil-induced currents (K i ¼ 177 mM) and the 500 mM diazoxide-induced currents (high-affinity site, K i1 ¼ 5 nM; low-affinity site, K i2 ¼ 108 mM) at À50 mV. 4 Application of tolbutamide (p100 mM) reversibly caused an inhibition of the 500 mM diazoxideinduced current at -50 mV. 5 MCC-134, a SUR type-specific K ATP channel regulator (1 -100 mM), produced a concentrationdependent inward K + current, which was suppressed by the application of glibenclamide at À50 mV. The amplitude of the MCC-134 (100 mM)-induced current was approximately 50% of that of the 100 mM pinacidil-induced currents. 6 Using cell-attached configuration, MCC-134 activated a glibenclamide-sensitive K ATP channel which was also activated by pinacidil. 7 RT -PCR analysis demonstrated the presence of SUR1 and SUR2B transcripts in pig urethra. 8 These results indicate that both SUR1 and SUR2B subunits play a functional role in regulating the activity of pig urethral K ATP channels and that SUR1 contributes less than 25% to total K ATP currents.

Novel and Established Potassium Channel Openers Stimulate Hair Growth In Vitro: Implications for their Modes of Action in Hair Follicles

“…Overall, this would suggest that both SUR1/Kir6.2-and SUR2B/Kir6.2-based K ATP channels are involved in hair follicle growth. This parallels a recent report that pig urethra contains both SUR1 and SUR2B potassium channels (Yunoki et al, 2003). Based on all current knowledge, it seems feasible to hypothesize that potassium channel regulators acting via SUR 2B may influence hair growth via the dermal papilla, whereas those acting via SUR1 receptors such as NNC 55-0118 may act directly on the keratinocytes of the follicle.…”

ATP-Sensitive Potassium Channels

“…A more recent study in colonic smooth muscle has detected the transcript for Kir6.1 and the authors propose that the K ATP channel here also comprises Kir6.1/SUR2B [122]. In pig urethra, where the unitary conductance is somewhat larger (43 pS), Yunoki et al [123] have suggested that K ATP may have a heteromeric Kir6.1/Kir6.2 pore structure, and also suggest on the basis of pharmacological studies that most channels may form with homomultimeric SUR2B subunits, while a subpopulation contain SUR1 multimers. The effects of genetic disruption of Kir6.1, Kir6.2, or SURs on K ATP channels of smooth muscle in urinary tract, GI tract, or airways would clarify the nature of these channels, but have not yet been reported.…”

Ion channels of the mammalian urethra

“…heterotetrameric) channel of K ir 6.1 and K ir 6.2 subunits, since the observed conductance value of 43 pS was intermediate between those measured for homomeric channels consisting of either K ir 6.1 or 6.2 subunits. [47][48][49][50] It has recently been definitively reported that the pore-forming region of the urethral smooth muscle K ATP channel is in fact a heterotetrameric complex of K ir 6.1 and K ir 6.2 subunits, arranged in a 3:1 ratio (Fig. 2).…”