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Inhibition of M-Type K+ and IM-Type Ca2+ Channels by the Human Gonadotropin-Releasing-Hormone Receptor Heterologously Expressed in Adult Neurons
- Source :
- Neuroendocrinology. 66:235-245
- Publication Year :
- 1997
- Publisher :
- S. Karger AG, 1997.
-
Abstract
- Gonadotropin-releasing hormone (GnRH) controls all aspects of reproductive function. GnRH is secreted by hypothalamic neurons and exerts its effects on the endocrine system through pituitary gonadotropes, while its effects on sexual receptivity are mediated by the central nervous system. The electrophysiological responses of central neurons to GnRH have shown both excitatory and inhibitory responses, but little is known about the mechanisms by which GnRH can change neuronal excitability. The present study addresses the mechanisms whereby stimulation of the human GnRH receptor changes neuronal excitability by using a combination of electrophysiological and heterologous expression techniques. Microinjection of in vitro transcribed cRNA coding for the human GnRH receptor into enzymatically dissociated adult rat superior cervical ganglion neurons resulted in GnRH receptor expression. Activation of the GnRH receptor inhibited both M-type K+ and N-type Ca2+ channels. Inhibition of M-type K+ channels was insensitive to pertussis toxin pretreatment and blocked by intracellular GDPbetaS. Inhibition of Ca2+ channels was slow in onset, voltage independent and insensitive to pertussis toxin. Wash-out of GnRH resulted in an unusual transient reversal of tonic G-protein-mediated Ca2+ channel inhibition. Block of the N-type Ca2+ channel with omega-conotoxin GVIA decreased Ca2+ current inhibition from 43 to 15%, indicating that the N-type Ca2+ channel is an effector target. Ca2+ channel inhibition was completely abolished by including a Ca2+ chelator in the patch pipette. Cell-attached macropatch experiments indicated that Ca2+ channel inhibition is mediated by a diffusible second messenger. These results demonstrate that the human GnRH receptor can inhibit M-type K+ and N-type Ca2+ channels when heterologously expressed in adult rat neurons. Modulation of M-type K+ and N-type Ca2+ channels in central neurons which contain GnRH receptors is likely to contribute to the changes in neuronal excitability elicited by GnRH.
- Subjects :
- endocrine system
medicine.medical_specialty
Voltage-dependent calcium channel
Endocrine and Autonomic Systems
Endocrinology, Diabetes and Metabolism
Potassium channel blocker
Gonadotropin-releasing hormone
Biology
Pertussis toxin
Gonadotropic cell
Cellular and Molecular Neuroscience
Endocrinology
Internal medicine
medicine
Excitatory postsynaptic potential
Receptor
hormones, hormone substitutes, and hormone antagonists
Gonadotropin-releasing hormone receptor
medicine.drug
Subjects
Details
- ISSN :
- 14230194 and 00283835
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Neuroendocrinology
- Accession number :
- edsair.doi...........eeb3aa59a077ce9235aed3f3c353f398