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¹ Laboratory of Neurobiology, Health Sciences, NIH, DHHS, PO Box 12233, Research Triangle Park, NC 27709, USA

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 7-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 7- and non-7-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 ([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 [Ca²⁺]_i/Q ratio was significantly larger (i.e. more than twice as big) for responses activated by NMDA than for 7-containing nAChRs in interneurones; the activation of the non-7 nAChRs did not produce any significant increase in [Ca²⁺]_i. Interestingly, the Ca²⁺ permeability of native 7 nAChRs in PC12 cells was significantly larger than in hippocampal interneurones, and not significantly different from NMDA receptors. Therefore, the 7-containing nAChRs in rat hippocampal interneurones are significantly less permeable to Ca²⁺ than not only NMDA receptors but also 7 nAChRs in PC12 cells.

(Received 3 May 2005; accepted after revision 27 May 2005; first published online 2 June 2005)
Corresponding author J. L. Yakel: NIEHS, F2-08, PO Box 12233, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. Email: yakel{at}niehs.nih.gov

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