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Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist.

ABSTRACT: The affinity of cGMP-gated ion channels (CNGCs) for cGMP in chick retinal cone photoreceptors is under circadian control. Here we report that dopamine (DA) and D2 receptor agonists evoke phase-dependent shifts in the affinity of CNGCs for activating ligand. Inside-out patch recordings from cultured chick cones were performed at circadian time (CT) 4-7 and CT 16-19 on the second day of constant darkness. Exposing intact cells to DA or the D2 agonist quinpirole for 2 hr before patch excision caused a significant increase in the K(D) for cGMP during the night (CT 16-19) but had no effect during the day (CT 4-7). DA or quinpirole treatment had no effect on the Hill slope or the average number of channels per patch. The effect of DA was blocked by the D2 antagonist eticlopride and was not mimicked by D1 agonists or blocked by D1 antagonists. By contrast, a brief (15 min) exposure to DA or quinpirole caused a decrease in K(D) during the subjective day and had no effect during the subjective night. Thus, the effect of D2 agonists depends on both the duration of agonist exposure and the time of day. Application of DA or quinpirole evoked a transient activation of the MAP kinase Erk (extracellular signal-related kinase) during the day but caused a sustained inhibition during the night. Conversely, D2 agonists caused activation of Ca2+/calmodulin-dependent protein kinase II during the night and inhibited this enzyme during the day. A circadian oscillator in cones appears to regulate the nature of the transduction cascade used by D2 receptors.

SUBMITTER: Ko GY

PROVIDER: S-EPMC2667621 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist.

Ko Gladys Y-P GY Ko Michael L ML Dryer Stuart E SE

The Journal of neuroscience : the official journal of the Society for Neuroscience 20030401 8

The affinity of cGMP-gated ion channels (CNGCs) for cGMP in chick retinal cone photoreceptors is under circadian control. Here we report that dopamine (DA) and D2 receptor agonists evoke phase-dependent shifts in the affinity of CNGCs for activating ligand. Inside-out patch recordings from cultured chick cones were performed at circadian time (CT) 4-7 and CT 16-19 on the second day of constant darkness. Exposing intact cells to DA or the D2 agonist quinpirole for 2 hr before patch excision cause ...[more]

PMID: 12716922

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Project description:Voltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance. In addition to phosphorylation sites, both Nav1.4 and Nav1.5 possess potentially regulatory binding sites for Ca2+ and/or the Ca2+-sensor calmodulin in their inactivating III-IV linker and C-terminal domains (CTD), where mutations are associated with a range of skeletal and cardiac muscle diseases. We summarize in vitro cell-attached patch clamp studies reporting correspondingly diverse, direct and indirect, Ca2+ effects upon maximal Nav1.4 and Nav1.5 currents (Imax) and their half-maximal voltages (V1/2) characterizing channel gating, in cellular expression systems and isolated myocytes. Interventions increasing cytoplasmic [Ca2+]i down-regulated Imax leaving V1/2 constant in native loose patch clamped, wild-type murine skeletal and cardiac myocytes. They correspondingly reduced action potential upstroke rates and conduction velocities, causing pro-arrhythmic effects in intact perfused hearts. Genetically modified murine RyR2-P2328S hearts modelling catecholaminergic polymorphic ventricular tachycardia (CPVT), recapitulated clinical ventricular and atrial pro-arrhythmic phenotypes following catecholaminergic challenge. These accompanied reductions in action potential conduction velocities. The latter were reversed by flecainide at RyR-blocking concentrations specifically in RyR2-P2328S as opposed to wild-type hearts, suggesting a basis for its recent therapeutic application in CPVT. We finally explore the relevance of these mechanisms in further genetic paradigms for commoner metabolic and structural cardiac disease.

Dataset Information

Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist.

Publications

Circadian phase-dependent modulation of cGMP-gated channels of cone photoreceptors by dopamine and D2 agonist.

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