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Pacemaker channels in mouse thalamocortical neurones are regulated by distinct pathways of cAMP synthesis
Author(s) -
Frère Samuel G. A.,
Lüthi Anita
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.050989
Subject(s) - gabab receptor , picrotoxin , chemistry , long term potentiation , gabaa receptor , receptor , neurotransmission , stimulation , inhibitory postsynaptic potential , neuroscience , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry
A crucial aspect of pacemaker current ( I h ) function is the regulation by cyclic nucleotides. To assess the endogenous mechanisms controlling cAMP levels in the vicinity of pacemaker channels, I h regulation by G‐protein‐coupled neurotransmitter receptors was studied in mouse thalamocortical neurones. Activation of β‐adrenergic receptors with (−)‐isoproterenol (Iso) led to a small steady enhancement of I h amplitude, whereas activation of GABA B receptors with (±)‐Baclofen (Bac) reduced I h , consistent with an up‐ and down‐regulation of basal cAMP levels, respectively. In contrast, a transient (τ decay , ∼200 s), supralinear up‐regulation of I h was observed upon coapplication of Iso and Bac that was larger than that observed with Iso alone. This up‐regulation appeared to involve a cAMP synthesis pathway distinct from that recruited by Iso, as it was associated with a reversible acceleration in I h activation kinetics and an occlusion of modulation by photolytically released cAMP, yet showed an 11 mV as opposed to a 6 mV positive shift in the activation curve and an at least seven‐fold increase in duration. GABA, in the presence of the GABA A antagonist picrotoxin, mimicked, whereas N‐ethylmaleimide, an inhibitor of G i ‐proteins, blocked the up‐regulation, supporting a requirement for GABA B receptor activation in the potentiation. Activation of synaptic GABA B responses via stimulation of inhibitory afferents from the nucleus reticularis potentiated Iso‐induced increments in I h , suggesting that synaptically located receptors couple positively to cAMP synthesis induced by β‐adrenergic receptors. These findings indicate that distinct pathways of cAMP synthesis target the pacemaker current and the recruitment of these may be controlled by GABAergic activity within thalamic networks.