2 results
Activation of NMDA receptor-channels in human retinal Müller glial cells inhibits inward-rectifying potassium currents
- Donald G. Puro, Joseph P. Yuan, Nikolaus J. Sucher
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- Journal:
- Visual Neuroscience / Volume 13 / Issue 2 / March 1996
- Published online by Cambridge University Press:
- 02 June 2009, pp. 319-326
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Although it is well known that neurotransmitters mediate neuron-to-neuron communication, it is becoming clear that neurotransmitters also affect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agonist N-methyl-D-aspartate (NMDA) on Müller cells, the predominant glia of the retina. Our immunocytochemical studies and immunodetection by Western blotting with monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the expression by human Müller cells of this essential component of NMDA receptor-channels. Under conditions in which potassium currents were blocked, NMDA-induced currents could be detected in perforated-patch recordings from cultured and freshly dissociated human Müller cells. These currents were inhibited by competitive and non-competitive blockers of NMDA receptor-channels. Extracellular magnesium reduced the NMDA-activated currents in a voltage-dependent manner. However, despite a partial block by magnesium, Müller cells remained responsive to NMDA at the resting membrane potential. Under assay conditions not blocking K+ currents, exposure of Müller cells to NMDA was associated with an MK-801 sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calcium since the inhibition of IK(IR) was significantly reduced when calcium was removed from the bathing solution or when the Müller cells contained the calcium chelator, BAPTA. Inhibition of the Müller cell KIR channels by the neurotransmitter glutamate is likely to have significant functional consequences for the retina since these ion channels are involved in K+ homeostasis, which in turn influences neuronal excitability.
Dopamine activates ATP-sensitive K+ currents in rat retinal pericytes
- DAVID M. WU, HAJIME KAWAMURA, QING LI, DONALD G. PURO
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- Journal:
- Visual Neuroscience / Volume 18 / Issue 6 / November 2001
- Published online by Cambridge University Press:
- 20 May 2002, pp. 935-940
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The relatively sparse vasculature of the retina minimizes obstruction to incoming light, but also poses a challenge to fulfilling the metabolic demands of retinal neurons. An efficient process for distributing energy supplies to areas of need is likely to involve neuron-derived vasoactive signals. However, knowledge of the mechanisms by which capillary perfusion is regulated by neuron-to-vascular signaling is limited. Potential targets of vasoactive molecules released from nerve cells are the pericytes, which are positioned on the endothelial walls of microvessels and are thought to play a role in controlling the microcirculation. In this study, we assessed the effect of dopamine on pericyte physiology. Because dopaminergic neurites are closely associated with microvessels that express dopamine receptors, this molecule is a putative neuron-to-capillary signal, as well as neurotransmitter. We used the perforated-patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on microvessels freshly isolated from the adult rat retina. In 43% (58/134) of the sampled pericytes, we found that dopamine reversibly activated a hyperpolarizing current, which increased the membrane potential by 19 ± 1 mV. This dopamine-induced current was inhibited by the ATP-sensitive potassium (KATP) channel blocker, glibenclamide. Consistent with a signaling pathway involving D1 dopamine receptors, adenylate cyclase and protein kinase A (PKA), the selective D1 antagonist, SCH23390, inhibited the hyperpolarizing effect of dopamine; the activator of adenylate cyclase, forskolin, mimicked the dopaminergic effect, and H89, which inhibits PKA, significantly reduced the hyperpolarization induced by dopamine. Taken together, our experiments indicate that a mechanism involving D1 dopamine receptors, adenylate cyclase, and PKA activates KATP currents in retinal pericytes. Our observations support the hypothesis that, in addition to being a neuromodulator, dopamine also serves as a signal linking neuronal activity with the function of the pericyte-containing microvasculature.