Amitriptyline modulation of Na+ channels in rat dorsal root ganglion neurons

The effects of amitriptyline, a tricyclic antidepressant, on tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurons were studied using the whole-cell patch damp method. Amitriptyline blocked both types of Na+ currents in a dose-and holding potential-dependent manner. At the holding potential of -80 mV, the apparent dissociation constants (K-d) for amitriptyline to block tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ channels were 4.7 and 105 mu M, respectively. These values increased to 181 and 193 mu M, respectively, when the membrane was held at a potential negative enough to remove the steady-state inactivation. Amitriptyline dose-dependently shifted the steady-state inactivation curves in the hyperpolarizing direction and increased the values of the slope factors for both types of Na+ channels. The voltage dependence of the activation of both types of Na+ channels was shifted in the depolarizing direction. It was concluded that amitriptyline blocked the two types of Na+ channels in rat sensory neurons by modulating the activation and the inactivation kinetics. (C) 2000 Elsevier Science B.V. All rights reserved.