Muscarinic Enhancement of R-Type Calcium Currents in Hippocampal CA1 Pyramidal Neurons

Autor: J. B. Kuzmiski, Chao Tai, Brian A. MacVicar
Rok vydání: 2006
Předmět:
Zdroj: Journal of Neuroscience. 26:6249-6258
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.1009-06.2006
Popis: The “toxin-resistant” R-type Ca(2+) 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, Ca(2+) currents in hippocampal CA1 pyramidal neurons after N, P/Q, and L-type Ca(2+) currents selectively were blocked. M(1)/M(3) cholinergic receptors mediated the muscarinic stimulation of R-type Ca(2+) channels. The signaling pathway underlying the R-type enhancement was independent of intracellular [Ca(2+)] changes and required the activation of a Ca(2+)-independent PKC pathway. Furthermore, we found that the enhancement of R-type Ca(2+) currents resulted in the de novo appearance of Ca(2+) spikes and in remarkable changes in the firing pattern of R-type Ca(2+) spikes, which could fire repetitively in the theta frequency. Therefore, muscarinic enhancement of R-type Ca(2+) channels could play an important role in modifying the dendritic response to synaptic inputs and in the intrinsic resonance properties of neurons.
Databáze: OpenAIRE