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PubMedDate not supplied

Expression and function of colonic epithelial KvLQT1 K+ channels.

1. KvLQT1 (KCNQ1) is a voltage-gated K+ channel essential for repolarization of the heart action potential. Defects in ion channels have been demonstrated in cardiac arrhythmia. This channel is inhibited potently by the chromanol 293B. The same compound has been shown to block cAMP-dependent electrolyte secretion in rat and human colon. Therefore, it was suggested that a K+ channel similar to KvLQT1 is expressed in the colonic epithelium. 2. In the present paper, expression of KvLQT1 and its function in colonic epithelial cells is described. Reverse transcription-polymerase chain reaction analysis of rat colonic mucosa demonstrated expression of KvLQT1 in both crypt cells and surface epithelium. When expressed in Xenopus oocytes, KvLQT1 induced a typical delayed activated K+ current. 3. As demonstrated, the channel activity could be further activated by increases in intracellular cAMP. These and other data support the concept that KvLQT1 is forming a component of the basolateral cAMP-activated K+ conductance in the colonic epithelium.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

Ion channels in the thick ascending limb of Henle's loop.

The thick ascending limb of Henle's loop (TAL) is polarized with respect to its conductances. The luminal membrane contains a K+ conductance which is made up by the synchronous operation of 60- to 80-pS K+ channels. The basolateral membrane contains a chloride conductance. This conductance corresponds most likely to a 30- to 60-pS Cl- channel present in this membrane. Our knowledge on the properties of the K+ channels of these cells has been increased rapidly by patch clamp studies: these K+ channels are inwardly rectifying. They are highly selective for K+ over Na+, Li+ and many other cations. They do not conduct Rb+, Cs+, NH+4 or other larger cations. In fact, all these three cations as well as choline, tetraethylammonium, lidocaine, verapamil, diltiazem, quinine, quinidine and Ba2+ inhibit these K+ channels. As apparent from kinetic studies the mechanisms of inhibition are different for the various blockers. The TAL K+ channels are downregulated by increasing cytosolic Ca2+ activity. Cytosolic adenosine trisphosphate (ATP) has a similar effect. This ATP inhibition is Ca2+ dependent. The affinity to ATP is augmented by increasing Ca2+. Cytosolic alkalinity increases the open probability of these channels, and cytosolic acidification has the opposite effect. This pH dependence is very marked. A change by 0.2 pH units leads to a more than twofold change in the open-channel probability. The basolateral chloride conductance reflects the properties of an outwardly rectifying 30- to 60-pS Cl- channel. This channel behaves, in many respects, like the Cl- channels of a multitude of Cl- transporting epithelia. It is characterized by two open and two closed states. It is highly selective for Cl- as compared with larger anions, and it is inhibited reversibly by Cl- channel blockers such as 5-nitro-2-(3-phenylpropylamino)-benzoate.

Animals↗