Effects of arachidonic acid on sodium currents in rat dorsal root ganglion neurons.
The effects of arachidonic acid on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion neurons were assessed using the whole-cell patch-clamp method. Both sodium currents were modulated in a similar way by extracellular application of arachidonic acid. Arachidonic acid increased the currents at lower depolarizing potentials, while it suppressed the currents at higher depolarizing potentials and at less negative holding potentials. These effects were due to the shifts of both the conductance-voltage curve and the steady-state inactivation curve in the hyperpolarizing direction. Indomethacin, a cyclooxygenase inhibitor, suppressed the arachidonic acid-induced shift of the conductance-voltage curve but not that of the steady-state inactivation curve. 5,8,11,14-Eicosatetraynoic acid, a non-metabolizable arachidonic acid analog, failed to shift the conductance-voltage curve but still produced the shift of the steady-state inactivation curve. Thus it is assumed that the effect of arachidonic acid on the sodium channel activation is caused by the metabolite(s) of arachidonic acid. However, the effect on the steady-state sodium channel inactivation is exerted by arachidonic acid itself. It is suggested that arachidonic acid, by modulating sodium currents, may alter the excitability of sensory neurons depending on the resting membrane potential.
Lee
Geon Young
GY
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuk-Suk Dong, Dong-Jak Ku, 156-756, Seoul, South Korea.
Shin
Yong Kyoo
YK
Lee
Chung Soo
CS
Song
Jin-Ho
JH
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D016718:Arachidonic Acid