Expression of CaV3.2 T-type Ca2+ channels in a subpopulation of retinal type-3 cone bipolar cells

Abstract

Retinal bipolar cells and ganglion cells are known to possess voltage-gated T-type Ca2+ channels. Previous electrophysiological recording studies suggested that there is differential expression of different T-type Ca2+ channel α1 subunits among bipolar cells. The detailed expression patterns of the individual T-type Ca2+ channel subunits in the retina, however, remain unknown. In this study, we examined the expression of the Cav3.2 Ca2+ channel α1 subunit in the mouse retina using immunohistochemical analysis and patch-clamp recordings together with a Cav3.2 knock out (KO) mouse line. The specificity of a Cav3.2 Ca2+ channel antibody was first confirmed in recombinant T-type Ca2+ channels expressed in HEK (human embryonic kidney) cells and in Cav3.2 KO mice. Our immunohistochemical analysis indicates that the Cav3.2 antibody labels a subgroup of type-3 cone bipolar cells (CBCs), the PKAβII-immunopositive type-3 CBCs. The labeling was observed throughout the cell including dendrites and axon terminals. Our patch-clamp recording results further demonstrate that Cav3.2 Ca2+ channels contribute to the T-type Ca2+ current in a subpopulation of type-3 CBCs. The findings of this study provide new insights into understanding the functional roles of T-type Ca2+ channels in retinal processing.

Electrophysiological fingerprints of OFF bipolar cells in rat retina

“…These currents were sensitive to the L-type Ca 2+ channel blocker nifedipine ( Fig. 5D ) and are therefore most likely L-type Ca 2+ currents, similar to those encountered in mouse BC-3b 8 . The glutamate response of BC-3b displays a transient component as in BC-3a, with an average amplitude of 83 ± 10 pA and a time-to-peak of 91 ± 7 ms, and a long-lasting sustained component of smaller amplitude (7 ± 1 pA, n = 27; Fig.…”

“…Within OFF BCs, the information is shaped by differential contributions of voltage-dependent Na + , Ca 2+ 8 9 and K + conductances 10 , including hyperpolarization-activated cyclic nucleotide-gated (HCN) channels 11 . Inhibitory signalling from different types of amacrine cells, mediated by GABA and glycine receptors 12 , as well as retinal neuromodulators like acetylcholine (ACh) and nitric oxide (NO) contribute to the conditioning of BC responses 13 14 .…”

CaV3.2 KO mice have altered retinal waves but normal direction selectivity

“…Glutamatergic waves are mediated by glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013), however which aspects of the circuit control burst properties and the frequency of waves are not yet identified. In the retina, T-type channels have been described in bipolar cell terminals and retinal ganglion cells (Ma & Pan, 2003; Pan et al , 2001; Lee et al , 2003; Hu et al , 2009; Cui et al , 2012; Sargoy et al , 2014). Hence, future experiments will be necessary to determine whether these changes are due to changes in the pacemaking or release properties from bipolar cells or in the excitability of RGCs.…”

Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics

“…The literature review in Van Hook et al, 2019 suggests that T-type calcium channels might be exclusively expressed in BC3. In mouse BC3b, the simultaneous expression of both and has been described ( Cui et al, 2012 ). Furthermore, the latter and other studies ( Hu et al, 2009 ; Satoh et al, 1998 ) suggest that voltage-gated calcium channels might not be located in the axon terminals only, but also in the soma and might play a role in signal transmission within the cell.…”