Role of voltage-gated Na+ and Ca2+ channels in gonadotropin-releasing hormone-induced membrane potential changes in identified rat gonadotropes.
We have previously reported that GnRH induces rhythmic hyperpolarizations in male rat (35- to 45-day-old) gonadotropes by periodically opening apamin-sensitive Ca(2+)-activated K+ channels. Using the whole cell recording technique, we now show that these gonadotropes, identified with the reverse hemolytic plaque assay, express tetrodotoxin-sensitive Na+ channels and omega-conotoxin-insensitive, high voltage-activated Ca2+ channels that are partially sensitive to dihydropyridines. We found no low voltage-activated Ca2+ channels in these cells. At the normal resting potential, about 93% of the Na+ channels and 50% of the Ca2+ channels are inactivated. The GnRH-induced hyperpolarizations transiently remove the resting inactivation of Na+ and Ca2+ channels, enabling them to initiate action potentials at the termination of each hyperpolarization. Opening of Na+ channels accounts for the high rate of rise and the positive peak of the action potential. In addition, a significant fraction of Ca2+ channels should be activated during the action potentials, allowing a voltage-gated entry of extracellular Ca2+ that can enhance the frequency and amplitude of GnRH-induced intracellular Ca2+ oscillations. Therefore, we envision the following role for action potentials in GnRH-stimulated Ca2+ responses: action potentials will open voltage-gated Ca2+ channels that allow entry of extracellular Ca2+, which can help to replenish the intracellular Ca2+ store and act as a coactivator in the stimulation of intracellular Ca2+ release from the inositol 1,4,5-trisphosphate-sensitive store.
Tse
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Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
Hille
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D015222:Sodium Channels; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone