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Ambient Glutamate Promotes Paroxysmal Hyperactivity in Cortical Pyramidal Neurons at Amyloid Plaques via Presynaptic mGluR1 Receptors.
Cereb Cortex
October 2017
German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen-Straße 17, 81377 Munich, Germany.
Synaptic dysfunctions and altered neuronal activity play major role in the pathophysiology of Alzheimer's disease (AD), with underlying mechanisms largely unknown. We report that in the prefrontal cortex of amyloid precursor protein-presenilin 1 and APP23 AD mice, baseline activity of pyramidal cells is disrupted by episodes of paroxysmal hyperactivity. Induced by spontaneous EPSC bursts, these incidents are prevalent in neurons proximal to amyloid plaques and involve enhanced activity of glutamate with metabotropic effects.
View Article and Find Full Text PDFDependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance.
Mol Pharmacol
February 2010
National Institute of Child Health and Human Development, Bethesda, MD 20892-4510, USA.
Anterior pituitary cells fire action potentials and release cyclic nucleotides both spontaneously and in response to agonist stimulation, but the relationship between electrical activity and cyclic nucleotide efflux has not been studied. In these cells, a tetrodotoxin-resistant background N(+) conductance is critical for firing of action potentials, and multidrug resistance proteins (MRPs) MRP4 and MRP5 contribute to cyclic nucleotide efflux. Here, we show that abolition of the background Na(+) conductance in rat pituitary cells by complete or partial replacement of extracellular Na(+) with organic cations or sucrose induced a rapid and reversible hyperpolarization of cell membranes and inhibition of action potential firing, accompanied by a rapid inhibition of cyclic nucleotide efflux.
View Article and Find Full Text PDFComparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice.
Br J Pharmacol
January 2009
Physiology, Division of Basic Medical Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast, Northern Ireland, UK.
Background And Purpose: W/W(v) and wild-type murine bladders were studied to determine whether the W/W(v) phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).
Experimental Approach: Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.
Key Results: Wild-type and W/W(v) detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology.
Cell type-specific expression of a genetically encoded calcium indicator reveals intrinsic calcium oscillations in adult gonadotropin-releasing hormone neurons.
J Neurosci
January 2007
Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
The gonadotropin-releasing hormone (GnRH) neurons exhibit a unique pattern of episodic activity to control fertility in all mammals. To enable the measurement of intracellular calcium concentration ([Ca2+]i) in adult GnRH neurons in situ, we generated transgenic mice in which the genetically encodable calcium indicator ratiometric Pericam was expressed by approximately 95% of GnRH neurons. Real-time monitoring of [Ca2+]i within adult male GnRH neurons in the acute brain slice revealed that approximately 70% of GnRH neurons exhibited spontaneous, 10-15 s duration [Ca2+]i transients with a mean frequency of 7 per hour.
View Article and Find Full Text PDFFundamental importance of Na+-Ca2+ exchange for the pacemaking mechanism in guinea-pig sino-atrial node.
J Physiol
March 2006
University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK.
Na+-Ca2+ exchange (NCX) current has been suggested to play a role in cardiac pacemaking, particularly in association with Ca2+ release from the sarcoplasmic reticulum (SR) that occurs just before the action potential upstroke. The present experiments explore in more detail the contribution of NCX to pacemaking. Na+-Ca2+ exchange current was inhibited by rapid switch to low-Na+ solution (with Li+ replacing Na+) within the time course of a single cardiac cycle to avoid slow secondary effects.
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