QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.106385v1 319/1/376    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Santos, H. R. Articles by Castro, N. G. Search for Related Content PubMed PubMed Citation Articles by Santos, H. R. Articles by Castro, N. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL GLUTAMIC ACID HYDROCHLORIDE POTASSIUM CHLORIDE TETRODOTOXIN

NEUROPHARMACOLOGY

The Magnitude of 7 Nicotinic Receptor Currents in Rat Hippocampal Neurons Is Dependent upon GABAergic Activity and Depolarization

Departmento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro, Brazil (H.R.S., H.S.R., P.S.-P., E.X.A., N.G.C.); and Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland (E.X.A.)

Hippocampal 7^* nicotinic acetylcholine receptors modulate the release of GABA and glutamate. The control of functional receptor pools by cell firing or synaptic activity could therefore allow for a local adjustment of the sensitivity to cholinergic input upon changes in neuronal activity. We first investigated whether tonic depolarization or cell firing affected the function of 7^*. The amplitude of 7^*-gated whole-cell currents in cultured rat hippocampal neurons exposed to high-extracellular K⁺ (40 mM KCl) for 24 to 48 h increased 1.3 to 5.5 times. The proportion of 7^*-responsive neurons (99%), the potency of acetylcholine, and the sensitivity to nicotinic antagonists were all unaffected. In contrast, block of spontaneous cell firing with tetrodotoxin for 24 h led to a 37% reduction in mean current amplitude. Reduced 7^* responses were seen after a 24-h blockade of N-type calcium channels but not of L-type calcium channels, N-methyl-D-aspartate (NMDA), or non-NMDA receptor channels, protein kinase C, or calcium-calmodulin kinases II and IV. The N-type or L-type calcium channel antagonists -conotoxin GVIA and nifedipine did not prevent the current-potentiating effect of KCl. The GABA_A antagonist picrotoxin led to a 44% reduction of the currents, despite increasing action potential firing, and also reversed the potentiating effect of KCl. Treatment with GABA, midazolam, or a GABA uptake blocker led to increased currents. These data indicate that 7^*-gated currents in hippocampal neurons are regulated by GABAergic activity and suggest that depolarization-induced GABA release may underlie the effect of increased extracellular KCl.

Address correspondence to: Dr. Edson X. Albuquerque, Department of Pharmacology and Experimental Therapeutics, UMAB, 655 West Baltimore Street, Baltimore, MD 21201-1559. E-mail: ealbuque{at}umaryland.edu