Role of Na⁺ and Ca²⁺ Channels in the Preoptic LH Surge Generating Mechanism in Proestrous Rats

Abstract

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 ip 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 μl saline containing the Na⁺ channel blocker tetrodotoxin (TTX) at a concentration of 1 μM, 2 μM, or 5 μM. Since 5 μM 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 μl of 5 μM 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 μl of 5 μM 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.