Mutant channels contribute ,50% to Na1 current in paramyotonia congenita muscle
نویسندگان
چکیده
An important question in the pathophysiology of dominantly inherited diseases, such as channelopathies, is the level of expression of the mutant protein. In our study, we address this issue by comparing the gating defects of two human muscle NaF channel mutants (R1448C and R1448P) causing paramyotonia congenita in native muscle specimens from two patients with those of the same mutant recombinant channels expressed in human embryonic kidney (HEK-293) cells. Patch-clamp recordings of transfected HEK-293 cells revealed a pronounced slowing of the NaF current decay, a leftshifted and decreased voltage dependence of steadystate inactivation, and an increased frequency of channel reopenings for mutant compared with wild-type channels.
منابع مشابه
Mutant channels contribute <50% to Na+ current in paramyotonia congenita muscle.
An important question in the pathophysiology of dominantly inherited diseases, such as channelopathies, is the level of expression of the mutant protein. In our study, we address this issue by comparing the gating defects of two human muscle Na+ channel mutants (R1448C and R1448P) causing paramyotonia congenita in native muscle specimens from two patients with those of the same mutant recombina...
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OBJECTIVE To electrophysiologically characterize the Na(v)1.4 mutant N440K found in a Korean family with a syndrome combining symptoms of paramyotonia congenita, hyperkalemic periodic paralysis, and potassium-aggravated myotonia. METHODS We characterized transiently expressed wild-type and mutant Na(v)1.4 using whole-cell voltage-clamp analysis. RESULTS N440K produced a significant depolari...
متن کاملPii: S0960-8966(99)00060-7
Effects of the antiarrhythmic and antimyotonic drug mexiletine were studied on two sodium channel mutants causing paramyotonia congenita (R1448H) and an overlap paramyotonic and hyperkalemic paralytic syndrome (M1360V). Channels were expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. Compared to the wild-type, channel, both ...
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BACKGROUND Myotonia and periodic paralysis caused by sodium channel mutations show variable responses to the anti-myotonic drug mexiletine. OBJECTIVE To investigate whether variability among sodium channel mutants results from differences in drug binding affinity or in channel gating. METHODS Whole-cell sodium currents (I(Na)) were recorded in tsA201 cells expressing human wild-type (WT) an...
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Three patients with paramyotonia congenita and 3 control persons were biopsied for an in vitro investigation of the sarcolemmal membrane parameters and of the contractile properties of paramyotonic muscle. At 37 degrees C, paramyotonic muscle fibers had normal resting potentials, but on cooling to 27 degrees C they depolarized. Depolarization to -60 mV caused spontaneous activity, and further d...
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