Essential role of the beta subunit in modulation of C‐class L‐type Ca2+ channels by intracellular pH

FEBS Letters

Klugbauer, Norbert¹  Schuhmann, Klaus³  Groschner, Klaus³  Hofmann, Franz¹  Romanin, Christoph²  Pflügelmeier, Helmut²  Höfer, Gerhard F²  Voelker, Christof³ 

[1] Insitut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany;Institut für Biophysik, Universität Linz, Linz, Austria;Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010 Graz, Austria

关键词: L-type Ca2+ channel;    β Subunit;    Intracellular pH;    Cellular regulation;    EGTA;    ethylene glycol bis (β-aminoethyl ether) N;    N;    N′;    N′-tetraacetic acid;    HEPES;    N-2-hydroxyethylpiperazine-N′-ethansulfonic acid;    pHe;    extracellular pH;    pHi;    intracellular pH;    P O;    a channel's probability of being in the open state;    P S;    a channel's probability to open upon a depolarisation;   

DOI  :  10.1016/S0014-5793(97)00391-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Elevation of intracellular pH (pH_i) enhances the activity of native L-type Ca²⁺ channels in cardiac and smooth muscle. We studied the modulation by pH_i of expressed L-type Ca²⁺ channels comprised of either the α_1C subunits alone or of α_1C plus β_2a subunits. Ca²⁺ channels were expressed in human embryonic kidney cells (HEK 293) and pH_i was increased from a basal level of 7.3 to 8.3 by exposure of cells to NH₄Cl (20 mM) or by elevation of extracellular pH to 8.5. Elevation of pH_i enhanced the activity of Ca²⁺ channels derived by coexpression of α_1C and β_2a subunits. This alkalosis-induced stimulation of channel activity was mainly due to an increase in channel availability. Channels derived by expression of α_1C alone were not affected by intracellular alkalosis. Our results demonstrate that the pH_i sensitivity of L-type Ca²⁺ channels is conferred by the β subunit of the channel complex.

【 授权许可】

Unknown