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The Journal of Neuroscience, October 8, 2003, 23(27):9024-9031
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Cellular/Molecular
Functional Mapping and Ca2+ Regulation of Nicotinic Acetylcholine Receptor Channels in Rat Hippocampal CA1 Neurons
Leonard Khiroug,
Rashid Giniatullin,
Rebecca C. Klein,
Dmitriy Fayuk, and
Jerrel L. Yakel
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing  7-containing receptors thought to be Ca2+-permeable, are expressed in the CNS, where they appear to regulate cognitive processing and synaptic plasticity. To understand the physiological role of nAChRs in regulating neuronal excitability, it is important to know the distribution of functional receptors along the surface of neurons, whether they can increase [Ca2+]i, and/or are regulated by Ca2+. We mapped the distribution of receptors on the membrane of rat hippocampal CA1 stratum radiatum interneurons and pyramidal cells in acute slices by recording nAChR-mediated currents elicited by local UV laser-based photolysis of caged carbachol in patch-clamped neurons. The local application ( 7 µm patches) allowed mapping of functional nAChRs along the soma and dendritic tree, whereas the fast uncaging minimized the effects of desensitization of 7-containing nAChRs and allowed us to measure the kinetics of responses. The 7-containing nAChRs were the predominant subtype on interneurons, and were located primarily at perisomatic sites (<70 µm from the soma; in contrast to the more uniform distribution of glutamate receptors); no currents were detectable on pyramidal neurons. The activation of nAChRs increased [Ca2+]i, indicating that these native receptors in acute slices are significantly Ca2+-permeable, consistent with previous observations made with recombinant receptors. In addition, they exhibited strong desensitization, the rate of recovery from which was controlled by [Ca2+]i. Our results demonstrate the strategic location and Ca2+ regulation of 7-containing nAChRs, which may contribute to understanding their involvement in hippocampal plasticity.
Key words: nicotinic; acetylcholine; hippocampus; interneuron; patch clamp; channel
Received June 10, 2003;
revised August 11, 2003;
accepted August 14, 2003.
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