Modulation of voltage-dependent K+ currents (IK(V)) in retinal bipolar cells by ascorbate is mediated by dopamine D1 receptors.
Ascorbic acid (AA), a neuromodulator in the vertebrate CNS, is released from glutamatergic neurons in exchange with glutamate uptake and, in turn, modulates the release of both glutamate and dopamine. We have reported that voltage-gated K+ currents (IK(V)) in ON-mixed rod/cone bipolar cells (Mb) were suppressed 60% by 100-200 microM AA when added to an ascorbate-free solution. However, as the in vivo [AA]o in retina is about 200 microM, we studied the effects of changes in [AA]o on IK(V) when [AA]o was varied around a baseline concentration of 200 microM. Whole-cell currents were recorded with patch-clamp methods from goldfish Mb cells in retinal slices, bathed in a solution containing 200 microM AA. We found that (1) IK(V) was enhanced (180+/-36%, n = 9) by increases of [AA]o less than 40 microM with an average latency of 8 min. (2) However, IK(V) was suppressed without an appreciable latent period by two conditions: increases more than 40 microM [AA]o and decreases by any amount greater than 10 microM. (3) Effects of delta[AA]o on IK(V) were blocked by a D1 dopamine receptor antagonist, SCH 23390, but not by a D2 receptor antagonist, spiperone. Increased concentrations of a D1 agonist (SKF 38390) and dopamine had similar concentration-dependent effects on IK(V) as did AA, even in the presence of 200 microM ascorbate. Ascorbate has complicated concentration-dependent effects on IK(V) of Mb cells in vitro that were mediated by D1 dopamine receptors, suggesting that dopamine and ascorbate may be involved reciprocally in modulating IK(V), with consequences on the transmission of rod signals to the inner retina.
Fan
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Department of Neurobiology and Behavior, State University of New York at Stony Brook, 11794-5230, USA. sfan@neurobio.sunysb.edu
Yazulla
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D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006054:Goldfish / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D015221:Potassium Channels; D017447:Receptors, Dopamine D1; D001205:Ascorbic Acid