Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel.
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| Abstract |
Mutations in the human skeletal muscle Na+ channel underlie the autosomal dominant disease hyperkalemic periodic paralysis (HPP). Muscle fibers from affected individuals exhibit sustained Na+ currents thought to depolarize the sarcolemma and thus inactivate normal Na+ channels. We expressed human wild-type or M1592V mutant alpha-subunits with the beta1-subunit in Xenopus laevis oocytes and recorded Na+ currents using two-electrode and cut-open oocyte voltage-clamp techniques. The most prominent functional difference between M1592V mutant and wild-type channels is a 5- to 10-mV shift in the hyperpolarized direction of the steady-state activation curve. The shift in the activation curve for the mutant results in a larger overlap with the inactivation curve than that observed for wild-type channels. Accordingly, the current through M1592V channels displays a larger noninactivating component than does that through wild-type channels at membrane potentials near -40 mV. The functional properties of the M1592V mutant resemble those of the previously characterized HPP T704M mutant. Both clinically similar phenotypes arise from mutations located at a distance from the putative voltage sensor of the channel.
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| Authors | C V Rojas, A Neely, G Velasco-Loyden, V Palma, M Kukuljan |
| Journal | The American journal of physiology (Am J Physiol) Vol. 276 Issue 1 Pg. C259-66 (01 1999) ISSN: 0002-9513 [Print] United States |
| PMID | 9886942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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