Abstract
The molecular identity of K(+) channels involved in Ehrlich cell volume regulation is unknown. A background K(+) conductance is activated by cell swelling and is also modulated by extracellular pH. These characteristics are most similar to those of newly emerging TASK (TWIK-related acid-sensitive K(+) channels)-type of two pore-domain K(+) channels. mTASK-2, but not TASK-1 or -3, is present in Ehrlich cells and mouse kidney tissue from where the full coding sequences were obtained. Heterologous expression of mTASK-2 cDNA in HEK-293 cells generated K(+) currents in the absence intracellular Ca(2+). Exposure to hypotonicity enhanced mTASK-2 currents and osmotic cell shrinkage led to inhibition. This occurred without altering voltage dependence and with only slight decrease in pK(a) in hypotonicity but no change in hypertonicity. Replacement with other cations yields a permselectivity sequence for mTASK-2 of K(+) > Rb(+) Cs(+) > NH(4)(+) > Na(+) congruent with Li(+), similar to that for the native conductance (I(K, vol)). Clofilium, a quaternary ammonium blocker of I(K, vol), blocked the mTASK-2-mediated K(+) current with an IC(50) of 25 microm. The presence of mTASK-2 in Ehrlich cells, its functional similarities with I(K, vol), and its modulation by changes in cell volume suggest that this two-pore domain K(+) channel participates in the regulatory volume decrease phenomenon.
Highlights
Potassium channels are multimeric membrane proteins capable of allowing the passage of Kϩ ions across the membrane down their electrochemical potential gradient
The presence of mTASK-2 in Ehrlich cells, its functional similarities with IK, vol, and its modulation by changes in cell volume suggest that this two-pore domain K؉ channel participates in the regulatory volume decrease phenomenon
There was no detectable amplification of mTASK-1 using RNA from Ehrlich cells or from mouse liver, a negative control known to lack mTASK-1 mRNA [2, 22, 23]
Summary
Potassium channels are multimeric membrane proteins capable of allowing the passage of Kϩ ions across the membrane down their electrochemical potential gradient Their functions range from the propagation of the action potential and the control of excitability to transepithelial transport and the homeostasis of cell volume. From the molecular point of view, three major families have been distinguished [1]: voltage-gated KV channels, Kir inward rectifiers and SKCa/IKCa Ca2ϩ-dependent Kϩ channels. These previously described Kϩ channels have only one pore domain (P) and form tetramers with each monomer contributing one P domain to the selectivity filter. The best studied is TASK-1 (KCNK3), which is thought to be the background Kϩ conductance closed by neurotransmitters to enhance excitability in the central nervous system [4, 5]
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