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Voltage-gated Na+ channels display rapid activation gating (opening) as well as fast and slow inactivation gating (closing) during depolarization. We substituted residue S1759 (serine), a putative D4S6 gating hinge of human cardiac hNav1.5 Na+ channels with A (alanine), D (aspartate), K (lysine), L (leucine), P (proline), and W (tryptophan). Significant shifts in gating parameters for activation and...
Amitriptyline is a tricyclic antidepressant, which also alleviates various pain syndromes at its therapeutic plasma concentration (0.36-0.90 μM). Accumulated evidence suggests that such efficacy may be due to block of voltage-gated Na + channels. The Na + channel α-subunit protein consists of four homologous domains (D1-D4), each with six transmembrane segments (S1-S6). The aims of...
Recent reports suggest that four S6 C-termini may jointly close the voltage-gated cation channel at the cytoplasmic side, probably as an inverted teepee structure. In this study we substituted individually a total of 18 residues at D1S6 and D4S6 C-terminal ends of the rNav1.4 Na+ channel α-subunit with tryptophan (W) and examined their corresponding gating properties when expressed in Hek293t cells...
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