Changes of the excitability of rat trigeminal root ganglion neurons evoked by alpha(2)-adrenoreceptors.
The aim of the study was to examine the effects of alpha(2)-adrenoreceptor agonists on the excitability of trigeminal root ganglion (TRG) neurons using the perforated patch-clamp technique, and to determine whether these neurons express mRNA for alpha(2)-adrenoreceptors. In current-clamp mode, the resting membrane potential was -57.4+/-1.2 mV (n=26). Most neurons (71%) were hyperpolarized by clonidine (5-50 microM) in a concentration-dependent manner. The response was associated with an increase of cell input resistance. In addition, clonidine reduced the repetitive firing evoked by depolarizing current pulses. An alpha(2)-adrenergic agonist, UK14,304, (10-20 microM) also hyperpolarized TRG neurons. The clonidine- and UK14,304-induced hyperpolarization was blocked by idazoxan (alpha(2)-adrenoreceptor antagonist). In voltage-clamp, clonidine (1-50 microM) reversibly reduced the hyperpolarization- and time-dependent cationic current. The effect was mimicked by UK14,304 (10-20 microM), and antagonized by idazoxan. Hyperpolarization-activated cationic current was blocked by extracellular Cs(+) (2 mM) or a specific blocker, ZD7288 (20 microM). Analysis of tail currents revealed that a reversal potential of the clonidine-sensitive component of hyperpolarization-activated cationic current was -46 mV. Single-cell reverse transcription-polymerase chain reaction analysis demonstrated the expression of mRNA for alpha(2A)- and alpha(2C)-adrenoreceptors. These results demonstrate that activation of alpha(2)-adrenoreceptors can hyperpolarize TRG neurons, and that the inhibitory effect is associated with inhibition of hyperpolarization-activated cationic current. Our results suggest that activation of alpha(2)-adrenoreceptors in the absence of nerve injury may have an inhibitory effect on nociceptive transmission in the trigeminal system at the level of both TRG neuronal cell bodies and primary afferent terminals.
Takeda
M
M
Department of Physiology, School of Dentistry at Tokyo, Nippon Dental University, 1-9-20 Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan. m-takeda@tokyo.ndu.ac.jp
Ikeda
M
M
Tanimoto
T
T
Lipski
J
J
Matsumoto
S
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000068438:Brimonidine Tartrate; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*; D014277:Trigeminal Neuralgia / Q000378:metabolism / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D007473:Ion Channels; D020033:Protein Isoforms; D011810:Quinoxalines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D003000:Clonidine