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A human intermediate conductance calcium-activated potassium channel

Takahiro IshiiVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703Christopher SilviaVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703Birgit HirschbergVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703Chris T. BondVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703John P. AdelmanVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703James MaylieVollum Institute and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201; and ICAgen Corporation, Research Triangle Park, NC 27703
1997en
ABI

Аннотация

An intermediate conductance calcium-activated potassium channel, hIK1, was cloned from human pancreas. The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain. Expression of hIK1 in Xenopus oocytes gave rise to inwardly rectifying potassium currents, which were activated by submicromolar concentrations of intracellular calcium (K0.5 = 0.3 microM). Although the K0.5 for calcium was similar to that of small conductance calcium-activated potassium channels, the slope factor derived from the Hill equation was significantly reduced (1.7 vs. 3. 5). Single-channel current amplitudes reflected the macroscopic inward rectification and revealed a conductance level of 39 pS in the inward direction. hIK1 currents were reversibly blocked by charybdotoxin (Ki = 2.5 nM) and clotrimazole (Ki = 24.8 nM) but were minimally affected by apamin (100 nM), iberiotoxin (50 nM), or ketoconazole (10 microM). These biophysical and pharmacological properties are consistent with native intermediate conductance calcium-activated potassium channels, including the erythrocyte Gardos channel.

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