The Magnitude of α7 Nicotinic Receptor Currents in Rat Hippocampal Neurons Is Dependent upon GABAergic Activity and Depolarization

Abstract

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 ϩ (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 currentpotentiating 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.

Erythrina mulungu Alkaloids Are Potent Inhibitors of Neuronal Nicotinic Receptor Currents in Mammalian Cells

“…In all cases we used a near-EC 50 concentration of acetylcholine and a fixed, high concentration of alkaloids in single application experiments. Hippocampal neurons, which predominantly express α7* nicotinic acetylcholine receptors [19], [22], were stimulated by 100 µM acetylcholine and then concomitantly by acetylcholine and one of the three alkaloids also at 100 µM (Fig. 2A).…”

Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation

“…However, it is possible that GABA A R activation is weaker than the involvement of other excitatory receptors, such as nAChRs. For example, it has been shown in hippocampal slice preparations that the whole cell current induced by nAChR activation was increased after GABA release [ 63 ]. So, it is possible that ACh excitatory effect during VS alone [ 64 ] or VS/HDB did overcome the GABA A R activation by muscimol.…”

Beta (∼16 Hz) frequency neural oscillations mediate auditory sensory gating in humans

“…Using resting beta frequency power as a phenotype, Porjesz and colleagues (2002) report linkage disequilibrium of beta (16.5–20.0 Hz) EEG power to markers of a GABAa subunit gene. Notably, P50 suppression is modulated by alpha 7 nicotinic acetylcholine receptors located on GABAergic interneurons (Freedman et al, 1997; Hajos et al, 2005; Leonard et al, 1996; Santos, Ribeiro, Setti‐Perdigao, Albuquerque, & Castro, 2006) and may also involve glutamatergic mechanisms (Shepard, Joy, Clerkin, & Schwarcz, 2003). Sensory gating deficits have been associated with neuropsychiatric conditions including schizophrenia and alcoholism (Freedman et al, 1996; Marco, Fuentemilla, & Grau, 2005).…”