Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine.
To elucidate the local anesthetic mechanism of diphenhydramine, its effects on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion (DRG) neurons were examined by the whole-cell voltage clamp method. Diphenhydramine blocked TTX-S and TTX-R sodium currents with K(d) values of 48 and 86 microM, respectively, at a holding potential of -80 mV. It shifted the conductance-voltage curve for TTX-S sodium currents in the depolarizing direction but had little effect on that for TTX-R sodium currents. Diphenhydramine caused a shift of the steady-state inactivation curve for both types of sodium currents in the hyperpolarizing direction. The time-dependent inactivation became faster and the recovery from the inactivation was slowed by diphenhydramine in both types of sodium currents. Diphenhydramine produced a profound use-dependent block when the cells were repeatedly stimulated with high-frequency depolarizing pulses. The use-dependent block was more pronounced in TTX-R sodium currents. The results show that diphenhydramine blocks sodium channels of sensory neurons similarly to local anesthetics.
Kim
Y S
YS
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuk-Suk Dong, 156-756, Seoul, South Korea.
Shin
Y K
YK
Lee
C
C
Song
J
J
D000818:Animals; D004155:Diphenhydramine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D015222:Sodium Channels; D013779:Tetrodotoxin; D004155:Diphenhydramine