Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels.

The mammalian family of two-pore domain K+ (K2P) channel proteins are encoded by 15 KCNK genes and subdivided into six subfamilies on the basis of sequence similarities: TWIK, TREK, TASK, TALK, THIK, and TRESK. K2P channels are expressed in cells throughout the body and have been implicated in diverse cellular functions including maintenance of the resting potential and regulation of excitability, sensory transduction, ion transport, and cell volume regulation, as well as metabolic regulation and apoptosis. In recent years K2P channel isoforms have been identified as important targets of several widely employed drugs, including: general anesthetics, local anesthetics, neuroprotectants, and anti-depressants.

Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells.

Multiple genes of the TASK subfamily of two-pore domain K(+) channels are reported to be expressed in rat glomerulosa cells. To determine which TASK isoforms contribute to native leak channels controlling resting membrane potential, patch-clamp studies were performed to identify biophysical and pharmacological characteristics of macroscopic and unitary K(+) currents diagnostic of recombinant TASK channel isoforms. Results indicate K(+) conductance (gK(+)) is mediated almost exclusively by a weakly voltage-dependent (leak) K(+) channel closely resembling TASK-3.

Role of membrane depolarization and T-type Ca2+ channels in angiotensin II and K+ stimulated aldosterone secretion.

The hypothesis that Ca2+ influx necessary for angiotensin II (AngII) and K+ stimulation of aldosterone secretion is primarily mediated by membrane depolarization and activation of T-type Ca2+ channels was examined in isolated rat adrenal glomerulosa cells. Perforated-patch clamp recordings of membrane potential (Vm) demonstrated that AngII and K+ induce concentration-dependent depolarizations capable of activating T channels and, at high K+ and AngII concentrations, activating L channels and inactivating T channels. K+-induced depolarizations were stable and readily reversible.

Divalent cation permeability and blockade of Ca2+-permeant non-selective cation channels in rat adrenal zona glomerulosa cells.

1. The effects of the divalent cations Ca2+, Mg2+ and Ni2+ on unitary Na+ currents through receptor-regulated non-selective cation channels were studied in inside-out and cell-attached patches from rat adrenal zona glomerulosa cells. 2.

Effects of K+ channel blockers on K+ channels, membrane potential, and aldosterone secretion in rat adrenal zona glomerulosa cells.

The hypothesis that angiotensin II (ANG II)-induced aldosterone secretion is mediated through inhibition of plasma membrane K+ channels was examined by measuring the effects of K+ channel blockers on K+ currents, membrane potential, and aldosterone secretion in rat adrenal glomerulosa cells. Effective K+ channel blockers were identified and studied using patch clamp methods on isolated glomerulosa cells in cell culture. Extracellular Cs+ (2-20 mm) caused a voltage-dependent inhibition of macroscopic K+ currents, exhibiting an apparent Kd of 2 mM for blockade of K+ current at membrane potentials near the K+ equilibrium potential.