Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells

Abstract

The single channel properties of TASK-like oxygen-sensitive potassium channels were studied in rat carotid body type 1 cells. We observed channels with rapid bursting kinetics, active at resting membrane potentials. These channels were highly potassium selective with a slope conductance of 14-16 pS, values similar to those reported for TASK-1. In the absence of extracellular divalent cations, however, single channel conductance increased to 28 pS in a manner similar to that reported for TASK-3. After patch excision, channel activity ran down rapidly. Channel activity in inside-out patches was markedly increased by 2 and 5 mM ATP and by 2 mM ADP but not by 100 microM ADP or 1 mM AMP. In cell-attached patches, both cyanide and 2,4-dinitrophenol strongly inhibited channel activity. We conclude that 1) whilst the properties of this channel are consistent with it being a TASK-like potassium channel they do not precisely conform to those of either TASK-1 or TASK-3, 2) channel activity is highly dependent on cytosolic factors including ATP, and 3) changes in energy metabolism may play a role in regulating the activity of these background K+ channels.

A New Look at the Respiratory Stimulant Doxapram

“…Buckler established that oxygen sensing in the carotid body occurs through the inhibition of a baseline K + current that was not inhibited by conventional K + channel blockers (7). These characteristics conform closely to those members of the K 2P channel family responsible for background K + currents (54). Background potassium channels have been found important in setting the resting membrane potential of cells and to control the overall excitability of neurons in the CNS.…”

Melanoma cells exhibit strong intracellular TASK-3-specific immunopositivity in both tissue sections and cell culture

“…The molecular composition, biophysics and pharmacology of these channels have been thoroughly studied in the past few years, but (for obvious reasons) mostly in heterologous expression systems and in animal tissues. There are a number of physiological functions related to the activity of TASK-3 channels: they are responsible for the acidosis and hypoxia sensitivity of both the peripheral and central chemoreceptors [23,[31][32][33][34], and have important roles in the regulation of aldosterone secretion in the zona glomerulosa cells of the adrenal medulla [29]. They may have significance in the mediation of short-and long-term changes of neuronal excitability [1,[35][36][37][38][39][40][41], they may be involved in the neurone-glia interaction [42], and they may regulate cell apoptosis ( [15,16]; for a review see [43]).…”

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

“…Rat carotid body type 1 cells expressed TASK-1 and the predominant plasma membrane leak K + current type exhibited a unitary conductance, mean open time, voltage-independent open probability, and other pharmacological characteristics nearly identical to cloned TASK-1 [19,203]. Unlike cloned TASK-1 channels, however, these native channels were sensitive to extracellular Mg 2+ [203]. Reducing Mg 2+ from 3 mM to a nominally Mg 2+ -free saline (in Ca 2+ -free saline) doubled inward conductance from 13.8 pS to 28 pS without affecting outward conductance.…”

“…TASK-1-like and TASK-3-like currents have also been identified in cells where a single type of K + leak channel appears to predominate the plasma membrane despite data indicating expression of multiple K2P genes. Rat carotid body type 1 cells expressed TASK-1 and the predominant plasma membrane leak K + current type exhibited a unitary conductance, mean open time, voltage-independent open probability, and other pharmacological characteristics nearly identical to cloned TASK-1 [19,203]. Unlike cloned TASK-1 channels, however, these native channels were sensitive to extracellular Mg 2+ [203].…”

“…TASK channel closed states have not been systematically examined due to the difficulty in obtaining patches containing a single active channel and because of the short duration of the open and intraburst closed states [130,176]. Nevertheless, future studies need to address this aspect of channel gating as studies of native TASK channels have indicated that the lifetime of the interburst closed state is subject to both physiological and pharmacological modulation [134,203]. All TASK isoforms exhibited a low open probability at negative membrane potentials and only one study on gpTASK-3 reported that open probability, measured as NP o , was voltage-dependent, increasing with depolarization [178].…”