Heterogeneous expression of voltage-dependent Na⁺ and K⁺ channels in mammalian retinal bipolar cells

Abstract

Retinal bipolar cells show heterogeneous expression of voltage-dependent Na+ and K+ currents. We used whole-cell patch-clamp recordings to investigate the possible roles of these currents in the response properties of bipolar cells in rats. Isolated bipolar cells showed robust spontaneous regenerative activity, but the regenerative potential of rod bipolar cells reached a more depolarized level than that of cone bipolar cells. In both isolated cells and cells in retinal slices, the membrane depolarization evoked by current injection was apparently capped. The evoked membrane potential was again more depolarized in rod bipolar cells than in cone bipolar cells. Application of tetraethylammonium and 4-aminopyridine shifted the spontaneous regenerative potential as well as the evoked potential to a more depolarized level. In addition, a subclass of cone bipolar cells showed a prominent spike in the initial phase of the voltage response when the cells were depolarized from a relatively negative membrane potential. The spike was mediated mainly by tetrodotoxin-sensitive Na+ current. The presence of the spike sped up the response kinetics and enhanced the peak membrane potential. Results of this study raise the possibility that voltage-dependent K+ currents may play a role in defining different membrane operating ranges of rod and cone bipolar cells and that voltage-dependent Na+ currents may enhance the response kinetics and amplitude of certain cone bipolar cells.

Mechanism of High-Frequency Signaling at a Depressing Ribbon Synapse

“…These differences can originate from the cone synapse (DeVries, 2000), from voltage-dependent currents in the bipolar cell membrane (Ichinose et al, 2005; Ma et al, 2005; Puthussery et al, 2013; Saszik and DeVries, 2012), from inhibitory inputs at the bipolar cell terminal (Eggers and Lukasiewicz, 2011), or from a combination. The rapid recovery that we demonstrate originates in a specialized mechanism at the cone synapse because it persists when the bipolar cell is voltage-clamped and bathed in drugs that block amacrine cell synapses.…”

“…In current clamp without blockers, the transient at light-off may be enhanced or shaped by a momentary gap in inhibition at amacrine to bipolar cell synapses in the inner retina (Dong and Werblin, 1998; Lagnado, 1998). In addition, transient Off bipolar cell types in the mouse (Ma et al, 2005; Baden et al, 2013) and primate (Puthussery et al, 2013), but not the ground squirrel (Saszik and DeVries, 2012), express a voltage-dependent Na + current or another transient generating mechanism (Baden et al, 2013) that may amplify the responses at the cone synapse. Taken together, these results suggest that a combination of mechanisms may support high frequency signaling in Off bipolar cells.…”

The Neuronal Organization of the Retina

“…Another is a type of bipolar cell that generates Na + action potentials. Na + currents have been known to occur from studies of many retinas, but their functions are unclear (Ichinose and Lukasiewicz, 2007; Ichinose et al, 2005; Ma et al, 2005; Zenisek et al, 2001). In the ground squirrel, the structurally defined bipolar cell termed cb5b has a large tetrodotoxin (TTX)-sensitive Na + current.…”

Differential expression of three T-type calcium channels in retinal bipolar cells in rats

“…The existence of multiple bipolar cell types is believed to be the important anatomical substrates for segregating visual information into parallel pathways. Increasing evidence suggests that voltage-dependent membrane channels may contribute to the diverse physiological properties of bipolar cells (Burrone & Lagnado, 1997; Mao et al, 1998; Zenisek & Matthews, 1998; Protti et al, 2000; Ma et al, 2005). Among these channels, voltage-dependent Ca 2+ channels may be particularly important, since the activation of these channels could depolarize the membrane potentials and thereby shape the response waveform of bipolar cells, as well as initiate neurotransmitter release at their axon terminals.…”