Modulation of carbachol responsiveness in rat CA1 pyramidal neurons by corticosteroid hormones.
Pyramidal neurons in the rat CA1 hippocampal area contain membrane receptors for acetylcholine but also intracellular receptors for the adrenal corticosteroid hormone corticosterone, i.e., mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). In this in vitro study we investigated if occupation of MRs or GRs affects the responsiveness of CA1 pyramidal neurons to the cholinergic analogue carbachol. In slices from adrenally intact rats, where probably most of the MRs and a considerable degree of the GRs were occupied, carbachol (0.1-30 microM) induced a dose-dependent: (i) depolarization; (ii) reduction of the afterhyperpolarization and spike frequency accommodation associated with depolarizing current pulses; and (iii) reduction of the synaptically evoked EPSP, slow IPSP and (with higher doses) the fast IPSP. The carbachol responses in slices from adrenalectomized (ADX) rats, where both MRs and GRs are unoccupied, were generally similar to the responses in the adrenally intact controls. However, neurons recorded in slices from ADX rats 1-4 h after a brief (20 min) application of 3 nM aldosterone, thus predominantly occupying MRs, showed a significant reduction of the carbachol (1 microM) induced depolarization, when compared to the adrenally intact group. By contrast, neurons recorded in ADX slices treated with 30 nM corticosterone, inducing simultaneous activation of MRs and GRs, displayed significantly larger carbachol-evoked depolarizations (1 and 3 microM) than neurons in the three previous experimental groups. Carbachol-induced actions on the afterhyperpolarization, accommodation and synaptically evoked responses did not consistently depend on steroid receptor occupation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Graduate School for the Neurosciences, Department of Experimental Zoology, Faculty of Biology, University of Amsterdam, The Netherlands.
Joëls
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D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D002217:Carbachol; D000109:Acetylcholine