Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel

摘要: The voltage-sensitive sodium channel Nav1.5 (encoded by SCN5A) is expressed in electromechanical organs and mechanosensitive. This study aimed to determine the mechanosensitive transitions of at molecular level. was HEK 293 cells mechanosensitivity studied cell-attached patches. Patch pressure up −50 mmHg produced increases current large hyperpolarizing shifts voltage dependence with graded half-activation half-inactivation voltages (ΔV1/2) ∼0.7 mV mmHg−1. Voltage affected kinetics a single constant. suggested that stretch accelerated only one activation transitions. Stretch sensor movement, but not rate constants for gate opening fast inactivation. also appeared stabilize inactivated states, since recovery from inactivation slowed stretch. Unitary conductance maximum open probability were unaffected stretch, peak increased due an number active channels. effects partially reversible, following cycle required minutes. These data suggest mechanical results dose-dependent modulation sensors.