Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor α1 subunits (R528H)

FEBS Letters

Jurkat-Rott, Karin²  Melzer, Werner²  Pika-Hartlaub, Ursula²  Uetz, Ulrich²  Powell, Jeanne¹  Fontaine, Bertrand³  Lehmann-Horn, Frank² 

[1] Department of Biological Sciences, Smith College, Northampton, MA, USA;Abteilung für Angewandte Physiologie, Universität Ulm, D-89069 Ulm, Germany;Inserm CJF 9608, Fédération de Neurologie, Groupe Hôpitalier Pitié-Salpêtrière, 75013 Paris, France

关键词: Dihydropyridine receptor;    L-type calcium current;    Calcium transient;    Muscular dysgenesis mouse;    Human myotube;    Hypokalemic periodic paralysis;   

DOI  :  10.1016/S0014-5793(98)00090-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Rabbit cDNA of the α1 subunit of the skeletal muscle dihydropyridine (DHP) receptor was functionally expressed in a muscular dysgenesis mouse (mdg) cell line, GLT. L-type calcium currents and transients were recorded for the wild type and a mutant α1 subunit carrying an R528H substitution in the supposed voltage sensor of the second channel domain that is linked to a human disease, hypokalemic periodic paralysis. L-type channels expressed in GLT myotubes exhibited currents similar to those described for primary cultured mdg cells injected with rabbit wild type cDNA, indicating this system to be useful for functional studies of heterologous DHP receptors. Voltage dependence and kinetics of activation and inactivation of L-type calcium currents from mutant and wild type channels did not differ significantly. Intracellular calcium release activation measured by fura-2 microfluorimetry was not grossly altered by the mutation either. Analogous measurements on myotubes of three human R528H carriers revealed calcium transients comparable to controls while the voltage dependence of both activation and inactivation of the L-type current showed a shift to more negative potentials of approximately 6 mV. Similar effects on the voltage dependence of the fast T-type current and changes in the expression level of the third-type calcium current point to factors not primarily associated with the mutation perhaps participating in disease pathogenesis.

【 授权许可】

Unknown