Stable expression of human Kv1.3 potassium channels resets the resting membrane potential of cultured mammalian cells.
A cDNA clone encoding the human Kv1.3 potassium channel was stably expressed at high levels in a Chinese hamster ovary (CHO) cell line. The expressed currents strongly resemble those recorded from Xenopus oocytes injected with Kv1.3 cRNA, or from resting human T lymphocytes. One function ascribed to Kv1.3 in T lymphocytes is to stabilize the membrane potential, thereby regulating the Ca2+ signalling critical for mitogenic stimulation. In agreement with this hypothesis, we find that the heterologous expression of human Kv1.3 resets the resting potential of CHO cells, setting it to the threshold of activation of Kv1.3. An inhibitor of Kv1.3, margatoxin, depolarized transfected CHO cells to the potential of non-transfected cells. The combination of a steep voltage-dependence of activation with slow and incomplete inactivation appears to confer the ability of the Kv1.3 channel to 'clamp' the Vm of its host cells within a narrow range.
Defarias
F P
FP
Department of Membrane Biochemistry and Biophysics, Merck Research Labs, Rahway, NJ 07065, USA.
Stevens
S P
SP
Leonard
R J
RJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D051664:Kv1.3 Potassium Channel; D008564:Membrane Potentials / Q000235:genetics*; D009498:Neurotoxins / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection
C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C077910:margatoxin