Gating of skeletal and cardiac muscle sodium channels in mammalian cells. 1999

M F Sheets, and D A Hanck
The Nora Eccles Harrison Cardiovascular Research & Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA. michael@cvrti.uath.edu

1. Sodium channel ionic current (INa) and gating current (Ig) were compared for rat skeletal (rSkM1) and human heart Na+ channels (hH1a) heterologously expressed in cultured mammalian cells at approximately 13 C before and after modification by site-3 toxins (Anthopleurin A and Anthopleurin B). 2. For hH1a Na+ channels there was a concordance between the half-points (V ) of the peak conductance-voltage (G-V) relationship and the gating charge-voltage (Q-V) relationship with no significant difference in half-points. In contrast, the half-point of the Q-V relationship for rSkM1 Na+ channels was shifted to more negative potentials compared with its G-V relationship with a significant difference in the half-points of -8 mV. 3. Site-3 toxins slowed the decay of INa in response to step depolarizations for both rSkM1 and hH1a Na+ channels. The half-point of the G-V relationship in rSkM1 Na+ channels was shifted by -8.0 mV while toxin modification of hH1a Na+ channels produced a smaller hyperpolarizing shift of the V by -3.7 mV. 4. Site-3 toxins reduced maximal gating charge (Qmax ) by 33% in rSkM1 and by 31% in hH1a, but produced only minor changes in the half-points and slope factors of their Q-V relationships. In contrast to measurements in control solutions, after modification by site-3 toxin the half-points of the G-V and the Q-V relationships for rSkM1 Na+ channels demonstrated a concordance similar to that for hH1a. 5. Qmax vs. Gmax for rSkM1 and hH1a Na+ channels exhibited linear relationships with almost identical slopes, as would be expected if the number of electronic charges (e-) per channel was comparable. 6. We conclude that the faster kinetics in rSkM1 channels compared with hH1a channels may arise from inherently faster rate transitions in skeletal muscle Na+ channels, and not from major differences in the voltage dependence of the channel transitions.

UI MeSH Term Description Entries
D008322 Mammals Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young. Mammalia,Mammal
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D010210 Papillary Muscles Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000644 Quaternary Ammonium Compounds Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN Quaternary Ammonium Compound,Ammonium Compound, Quaternary,Ammonium Compounds, Quaternary,Compound, Quaternary Ammonium
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections

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