Properties and function of KCNQ1 K+ channels isolated from the rectal gland of Squalus acanthias

Abstract

KCNQ1 (KVLQT1) K+ channels play an important role during electrolyte secretion in airways and colon. KCNQ1 was cloned recently from NaCl-secreting shark rectal glands. Here we study the properties and regulation of the cloned sKVLQT1 expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells and compare the results with those obtained from in vitro perfused rectal gland tubules (RGT). The expression of sKCNQ1 induced voltage-dependent, delayed activated K+ currents, which were augmented by an increase in intracellular cAMP and Ca2+. The chromanol derivatives 293B and 526B potently inhibited sKCNQ1 expressed in oocytes and CHO cells, but had little effect on RGT electrolyte transport. Short-circuit currents in RGT were activated by alkalinization and were decreased by acidification. In CHO cells an alkaline pH activated and an acidic pH inhibited 293B-sensitive KCNQ1 currents. Noise analysis of the cell-attached basolateral membrane of RGT indicated the presence of low-conductance (<3 pS) K+ channels, in parallel with other K+ channels. sKCNQ1 generated similar small-conductance K+ channels upon expression in CHO cells and Xenopus oocytes. The results suggest the presence of low-conductance KCNQ1 K+ channels in RGT, which are probably regulated by changes in intracellular cAMP, Ca2+ and pH.

Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

“…It is unclear how this effect is mediated. However, high pH i activates Kv7.1 channels (KCNQ1) 31 , 32 , which may accelerate repolarization. The knowledge about the effects of high pH i on cardiac ion channels seems very limited.…”

Profile of IKs During the Action Potential Questions the Therapeutic Value of IKs Blockade

“…The current was detected also in other tissues, like vascular smooth muscle [16], embryonic xenopus muscle [17], vestibular dark cells [18], and pancreatic acinar cells [19]. Within a short period of time the current was identified in numerous vertebrate species, including shark [20], bullfrog [21,22], calf [23], rabbit [24], cat [25], guinea pig [26], dog [27] and men [28]. Sanguinetti and Jurkiewicz [29] demonstrated that the delayed rectifier current is composed of two distinct components namely; the rapid (I Kr ) and slow (I Ks ) components of I K .…”

Structural Requirements for Differential Sensitivity of KCNQ K+Channels to Modulation by Ca2+/Calmodulin

“…It was suggested that calcineurin mediates this Ca 2ϩ modulation of that M current (Marrion, 1996). Similarly conflicting are data on the Ca 2ϩ sensitivity of KCNQ1 or the cardiac I Ks K ϩ current (formed by KCNQ1 with its auxiliary subunit KCNE1), and it has been suggested that KCNQ1 can be inhibited (Shen and Marcus, 1998) or augmented (Kerst et al, 2001) by [Ca 2ϩ ] i , or indeed wholly Ca 2ϩ insensitive unless coexpressed with KCNE1 (Boucherot et al, 2001). These striking differences in the Ca 2ϩ sensitivity of KCNQ channels in different physiological systems suggest that Ca 2ϩ sensitivity is not an intrinsic property of KCNQ channels but rather the result of their interaction with Ca 2ϩ sensors, and so may depend on the nature of the available sensor, channel subunit composition and other physiological conditions.…”