Ca²⁺ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurones

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they are involved in a variety of physiological processes, including cognition and development. The nAChRs are ligand-gated cationic channels, and different subtypes are known to be differentially permeable to Ca²⁺; the α7-containing nAChRs are generally considered to be the most permeable. Ca²⁺ can activate and regulate a variety of signal transduction cascades, and the influx of Ca²⁺ through these receptors may have implications for synaptic plasticity. To determine the Ca²⁺ permeability of the nAChRs in rat hippocampal interneurones in the slice, which contain diverse subtypes of α7- and non-α7-containing nAChRs, we combined patch-clamp electrophysiology recordings with conventional fura-2 fluorescence imaging techniques. We estimated the relative Ca²⁺ permeability of the channels by determining the ratio of the increase in [Ca²⁺]_i level (Δ[Ca²⁺]_i) in the soma to the integrated transmembrane current (charge, Q) induced by the activation of the nAChRs, and compared this ratio to the highly Ca²⁺ permeable NMDA subtype of glutamate receptor channel. In all cells tested, the Δ[Ca²⁺]_i/Q ratio was significantly larger (i.e. more than twice as big) for responses activated by NMDA than for α7-containing nAChRs in interneurones; the activation of the non-α7 nAChRs did not produce any significant increase in [Ca²⁺]_i. Interestingly, the Ca²⁺ permeability of native α7 nAChRs in PC12 cells was significantly larger than in hippocampal interneurones, and not significantly different from NMDA receptors. Therefore, the α7-containing nAChRs in rat hippocampal interneurones are significantly less permeable to Ca²⁺ than not only NMDA receptors but also α7 nAChRs in PC12 cells.