Role of Na+ and Ca2+ channels in the preoptic LH surge generating mechanism in proestrous rats.
We studied whether Na+ and Ca2+ channels are involved in the neural mechanism responsible for the surge of gonadotropin-releasing hormone (GnRH) in proestrous rats. In experiment 1, female rats in proestrus were i.p. injected at 1345 h with pentobarbital sodium (35 mg/kg) to block spontaneous surge of LH and electrical stimulation was applied between 1400 and 1600 h to the preoptic area (POA) together with POA injection of 0.5 microl saline containing the Na+ channel blocker tetrodotoxin (TTX) at a concentration of 1 microM, 2 microM, or 5 microM. Since 5 microM TTX completely blocked the increase in serum LH concentrations evoked by the POA stimulation, we used this concentration in experiment 2 to observe the TTX effect on the spontaneous LH surge. In experiment 2, bilateral injections of 1.5 microl of 5 microM TTX at 1430 h in the POA in proestrous rats postponed the peak time and reduced the peak level of the LH surge. In experiment 3, bilateral injections of 1.5 microl of 5 microM L-type Ca2+ channel blocker nifedipine at 1430 h in the POA completely blocked the LH surge. Since the cell bodies of GnRH neurons are primarily concentrated in the POA in rats, these results suggest that both voltage-sensitive Na+ channels and Ca2+ channels contribute to the generation of action potentials at GnRH cell bodies for the surge release of GnRH.
Fukushima
Atsushi
A
Department of Physiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Sano
Akane
A
Aiba
Sachiko
S
Kimura
Fukuko
F
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007267:Injections; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009543:Nifedipine / Q000008:administration & dosage; D009994:Osmolar Concentration; D011301:Preoptic Area / Q000378:metabolism*; D011359:Proestrus / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000008:administration & dosage; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000008:administration & dosage
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D007987:Gonadotropin-Releasing Hormone; D013779:Tetrodotoxin; D007986:Luteinizing Hormone; D009543:Nifedipine