TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons

Abstract

The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked for major differences in dendritic morphology in neurons from TRPC1+/+ and TRPC1−/− mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes. Deletion of TRPC1 resulted in a modification of the shape of the current-voltage relationship, leading to an inward current increase. In current clamp recordings, the percentage of neurons that responded to depolarization in the presence of an mGluR I agonist with a plateau potential was increased in TRPC1−/− mice. There was also a small increase in the minor population of CA1 neurons that have more than one apical dendrite in TRPC1−/− mice. We conclude that TRPC1 has an inhibitory effect on receptor-operated nonselective cation channels in hippocampal CA1 neurons probably as a result of heterotetramer formation with other TRPC isoforms, and that TRPC1 deletion has only minor effects on dendritic morphology.

Transient Receptor Potential Canonical Channels in Health and Disease: A 2020 Update

“…TRPC1 has emerged as a hotspot for upcoming research, as it also seems to be involved in regulating hippocampal neurons [3,14], cardiac cell function [5,15], and contributes to cancer progression [13]. There is a long-lasting debate concerning whether TRPC1 can be considered an ion channel by itself or simply a modulatory subunit for other TRPC channels.…”

“…There is a long-lasting debate concerning whether TRPC1 can be considered an ion channel by itself or simply a modulatory subunit for other TRPC channels. For example, within the hippocampus, TRPC1 channels do not normally form functional homomers in the plasma membrane [3]. Instead, they are likely to form complexes with TRPC4 and TRPC5 [14].…”

“…TRPC4 and TRPC5 are activated in a PLCdependent pathway. Compared to TRPC4 and TRPC5 homodimers, heterodimers with TRPC1 are associated with a different shape in current-voltage relationship and a decreased permeability to calcium [3]. Recent experimental data suggested that TRPC1 and TRPC4 activation promoted neurotransmitter release at glutamatergic synapses in a calciumdependent manner [16].…”

“…TRPC1 and TRPC5 are thought to be involved in regulating neurite outgrowth and morphology [17,18]. To determine the role of TRPC1 with and without its heterodimeric counterparts TRPC4 and TRPC5 in the neurons of the CA1 region of the hippocampus, Kepura et al knocked out TRPC1 in these cells, while Arboit et al knocked out TRPC4/TRPC5 [3,14]. Taken together, these two different experiments provide a cohesive picture of TRPC1 involvement in the hippocampus as outlined below.…”