Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC5 , TRPC6

Title: Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?

Authors: Sameera Dasari, Joel Abramowitz, Lutz Birnbaumer, Allan T Gulledge

Journal, date & volume: Neuroreport, 2013 Jul 10 , 24, 550-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23652155

Abstract
Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a nonselective cation conductance that produces calcium-dependent 'afterdepolarizing potentials' (ADPs) following short trains of action potentials. Although the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient receptor potential (TRPC) channels, specifically the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate, flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC and that the focus of future work should be expanded to test the involvement of other potential ionic effectors.