Spontaneous regenerative activity in mammalian retinal bipolar cells: Roles of multiple subtypes of voltage-dependent Ca²⁺ channels

Abstract

Patch-clamp recordings were used to investigate the properties of the regenerative activity in acutely isolated bipolar cells from the rat retina. Spontaneous, pacemaker-like membrane potential oscillations were observed in all rod bipolar cells and the majority of cone bipolar cells. The waveform of the regenerative potential was stereotypical but distinct among different bipolar cell groups, especially between rod and cone bipolar cells. The spontaneous activity was completely blocked by Co2+, suggesting that Ca2+ influx through voltage-dependent Ca2+ channels was required for initiating such activity. Ca2+-induced Ca2+ release, however, was not found to be involved. The spontaneous activity was also blocked by mibefradil, a T-type Ca2+ channel antagonist. In contrast, application of nimodipine, an L-type Ca2+ current antagonist, affected mainly the waveform of the regenerative potential. This study shows that mammalian retinal bipolar cells in isolation are also capable of generating Ca2+-dependent spontaneous regenerative potential. However, T-type Ca2+ channels appear to be essential for the initiation of the spontaneous activity in mammalian bipolar cells.

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.…”

“…A critical component of the network mediating waves and a primary source of depolarizing input to RGCs is glutamate release from bipolar cells (Firl et al , 2013; Akrouh & Kerschensteiner, 2013). In the adult retina, bipolar cells exhibit unstable membrane potentials and their spontaneous depolarizations are mediated by low-voltage activated T-type calcium channels (Ma & Pan, 2003; Cueni et al , 2009; Sargoy et al , 2014; Puthussery et al , 2014) that are expressed in subsets of bipolar cells (Pan et al , 2001; Singer & Diamond, 2003) and of ganglion cells (Sargoy et al , 2014). The isoform α1 H (Ca V 3.2) of the T-type Ca 2+ channel (Cueni et al , 2009) localizes to cone bipolar cells.…”

Monopolar vs. bipolar subretinal stimulation—An in vitro study

“…The bipolar cells code neuronal signals by a depolarization of their membrane voltage. If an incoming depolarization reaches voltage gated Ca 2+ channels located at the axon terminal of the bipolar cells further signalling to amacrine and ganglion cells is initiated (Ma and Pan, 2003;Pan et al, 2001;Satoh et al, 1998). Numerical simulations have shown that subretinally applied electric fields can also depolarize the axon terminal of bipolar cells Gerhardt et al, 2010).…”

Active Roles of Electrically Coupled Bipolar Cell Network in the Adult Retina

“…It is generally accepted that retinal BCs respond to light stimulation with graded potentials (Werblin and Dowling, 1969;Kaneko, 1973). However, recent studies show that some types of BCs have the ability to generate Ca 2ϩ and/or Na ϩ spikes [Ca 2ϩ spikes: Burrone and Lagnado (1997), Zenisek and Matthews (1998), Protti et al (2000), Hull et al (2006), Palmer (2006), and Hu et al (2009); Na ϩ spikes: Ma et al (2005); Ca 2ϩ and Na ϩ spikes: Ma and Pan (2003)]. As Ca 2ϩ and/or Na ϩ spikes in BCs are much slower in time course than Na ϩ spikes in amacrine cells, it is intriguing to know how the electrically coupled BCs with such active membrane properties behave in the retina.…”