PT - JOURNAL ARTICLE AU - Hélio R. Santos AU - Helizane S. Ribeiro AU - Pedro Setti-Perdigão AU - Edson X. Albuquerque AU - Newton G. Castro TI - The Magnitude of α7 Nicotinic Receptor Currents in Rat Hippocampal Neurons Is Dependent upon GABAergic Activity and Depolarization AID - 10.1124/jpet.106.106385 DP - 2006 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 376--385 VI - 319 IP - 1 4099 - http://jpet.aspetjournals.org/content/319/1/376.short 4100 - http://jpet.aspetjournals.org/content/319/1/376.full SO - J Pharmacol Exp Ther2006 Oct 01; 319 AB - Hippocampal α7* 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 α7*. The amplitude of α7*-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 α7*-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 α7* 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 ω-conotoxin GVIA and nifedipine did not prevent the current-potentiating effect of KCl. The GABAA 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 α7*-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. The American Society for Pharmacology and Experimental Therapeutics