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Received April 25, 2007
Revised May 14, 2007
Accepted after revision May 14, 2007
7-containing nicotinic acetylcholine receptors in rat hippocampal neurons
1 NIEHS/NIH
* To whom correspondence should be addressed. E-mail: yakel{at}niehs.nih.gov.
Neuronal nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys-loop ligand-gated ion channels that are widely expressed in the brain. Among the many different subtypes of nAChRs known to be expressed in the rat brain, the
7-containing nAChRs are considered to be the most permeable to Ca2+. Utilizing highly localized and rapid iontophoretic agonist delivery, combined with patch-clamp electrophysiology and fura-2 fluorescent imaging techniques, we examined the
7 nAChR-mediated currents and [Ca2+]in transients in the dendrites of rat hippocampal CA1 interneurons in the slice. We found that in the dendrites, whereas the amplitudes of the current responses were smaller and the decay kinetics faster than the responses in the soma, the amplitudes of the [Ca2+]in signals were significantly larger. Cultured hippocampal neurons were studied since the dendritic field lies in the same focal plane, which allowed for a broader investigation of the spatiotemporal dynamics of [Ca2+]in signaling. In cultured neurons, the [Ca2+]in signals in the dendrites were similar to those in slices. Interestingly in cultures, even though the amplitude of the
7 nAChR-mediated currents dramatically decreased with distance from the soma (from ~20 to 250 µm), the amplitude of the [Ca2+]in signals did not correlate with distance. This indicates that the relative efficacy of
7 nAChR activation to increase [Ca2+]in levels in dendrites increased several fold with distance from the soma. These results may have implications for the role that
7 nAChRs have in regulating various signal transduction cascades, synaptic plasticity, and memory processes, via significant changes in [Ca2+]in levels.
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