| 11431495 |
Vega-Saenz de Miera E, Lau DH, Zhadina M, Pountney D, Coetzee WA, Rudy B: KT3.2 and KT3.3, two novel human two-pore K (+) channels closely related to TASK-1. J Neurophysiol. 2001 Jul;86(1):130-42.
We report the cloning of human KT3.2 and KT3.3 new members of the two-pore K (+) channel (KT) family. Based on amino acid sequence and phylogenetic analysis, KT3.2, KT3.3, and TASK-1 constitute a subfamily within the KT channel mammalian family. When Xenopus oocytes were injected with KT3.2 cRNA, the resting membrane potential was brought close to the potassium equilibrium potential. At low extracellular K (+) concentrations, two-electrode voltage-clamp recordings revealed the expression of predominantly outward currents. With high extracellular K (+) (98 mM), the current-voltage relationship exhibited weak outward rectification. Measurement of reversal potentials at different [K (+)](o) revealed a slope of 48 mV per 10-fold change in K (+) concentration as expected for a K (+)-selective channel. Unlike TASK-1, which is highly sensitive to changes of pH in the physiological range, KT3.2 currents were relatively insensitive to changes in intracellular or extracellular pH within this range due to a shift in the pH dependency of KT3.2 of 1 pH unit in the acidic direction. On the other hand, the phorbol ester phorbol 12-myristate 13-acetate (PMA), which does not affect TASK-1, produces strong inhibition of KT3.2 currents. Human KT3.2 mRNA expression was most prevalent in the cerebellum. In rat, KT3.2 is exclusively expressed in the brain, but it has a wide distribution within this organ. High levels of expression were found in the cerebellum, medulla, and thalamic nuclei. The hippocampus has a nonhomogeneous distribution, expressing at highest levels in the lateral posterior and inferior portions. Medium expression levels were found in neocortex. The KT3.2 gene is located at chromosome 8q24 1-3, and the KT3.3 gene maps to chromosome 20q13.1. |
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