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Keith J Buckler

Publications and source records attributed to Keith J Buckler.

6 recordsLinked to original sources
PubMed2006

The role of TASK-like K+ channels in oxygen sensing in the carotid body.

The carotid body plays an important role in initiating protective responses to hypoxemia. The primary oxygen sensing cells are the glomus or type 1 cells. Hypoxia evokes the secretion of neurotransmitters from these cells which then excite afferent nerves. This response is mediated via membrane depolarization and voltage-gated Ca2+ entry. Studies from this laboratory have revealed that membrane depolarization in response to hypoxia is primarily the result of inhibition of background K+ channels which show strong similarities to the acid sensitive tandem-P-domain K+ channels TASK-1 and TASK-3. The background K+ channels of type-1 cells are also very sensitive to inhibition of mitochondrial energy metabolism and, in excised patches, appear to be directly activated by ATP. Thus these TASK-like background channels would appear to confer the ability to sense changes in oxygen levels, pH and metabolism upon the type 1 cell. The key issue of whether the effects of hypoxia are mediated through changes in metabolism remains unanswered but the effects of inhibition of mitochondrial energy metabolism and of hypoxia upon background K+ channels is mutually exclusive suggesting that there is a close link between metabolism and oxygen sensing in the type 1 cell.

Animals↗
PubMed2003

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

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.

4-Aminopyridine↗