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The Journal of Neuroscience, June 7, 2006, 26(23):6249-6258; doi:10.1523/JNEUROSCI.1009-06.2006
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Cellular/Molecular
Muscarinic Enhancement of R-Type Calcium Currents in Hippocampal CA1 Pyramidal Neurons
Chao Tai,1 * J. Brent Kuzmiski,1,2 * andBrian A. MacVicar1 1Brain Research Center, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada, and 2Hotchkiss Brain Institute, Calgary, Alberta T2N 4N1, Canada
Correspondence should be addressed to Dr. Brian A. MacVicar, Brain Research Center, Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada. Email: bmacvica{at}interchange.ubc.ca
The "toxin-resistant" R-type Ca2+ channels are expressed widely in the CNS and distributed mainly in apical dendrites and spines. They play important roles in regulating signal transduction and intrinsic properties of neurons, but the modulation of these channels in the mammalian CNS has not been studied. In this study we used whole-cell patch-clamp recordings and found that muscarinic activation enhances R-type, but does not affect T-type, Ca2+ currents in hippocampal CA1 pyramidal neurons after N, P/Q, and L-type Ca2+ currents selectively were blocked. M1/M3 cholinergic receptors mediated the muscarinic stimulation of R-type Ca2+ channels. The signaling pathway underlying the R-type enhancement was independent of intracellular [Ca2+] changes and required the activation of a Ca2+-independent PKC pathway. Furthermore, we found that the enhancement of R-type Ca2+ currents resulted in the de novo appearance of Ca2+ spikes and in remarkable changes in the firing pattern of R-type Ca2+ spikes, which could fire repetitively in the theta frequency. Therefore, muscarinic enhancement of R-type Ca2+ channels could play an important role in modifying the dendritic response to synaptic inputs and in the intrinsic resonance properties of neurons.
Key words: acetylcholine; muscarinic; R-type calcium spikes;
1E calcium subunits; CaV2.3; T-type calcium currents; theta; epilepsy; oscillations; hippocampus
Received March 7, 2006; revised April 11, 2006; accepted May 1, 2006.
Correspondence should be addressed to Dr. Brian A. MacVicar, Brain Research Center, Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada. Email: bmacvica{at}interchange.ubc.ca
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