Differential effects of charybdotoxin on the activity of retinal ganglion cells in the dark- and light-adapted mouse retina

Abstract

Patch-clamp recordings were made from retinal ganglion cells in the mouse retina. Under dark adaptation, blockage of BKCa channels increases the spontaneous excitatory postsynaptic currents (EPSCs) and light-evoked On-EPSCs, while it decreases the light-evoked Off inhibitory postsynaptic currents (IPSCs). However, under light adaptation it decreases the light-evoked On-EPSCs, the spontaneous IPSCs and the light-evoked On- and Off-IPSCs. Blockage of BKCa channels significantly altered the outputs of RGCs by changing their light-evoked responses into a bursting pattern and increasing the light-evoked depolarization of the membrane potentials, while it did not significantly change the peak firing rates of light-evoked responses.

BK Channels Mediate Pathway-Specific Modulation of Visual Signals in theIn VivoMouse Retina

“…It cannot be excluded that BK channels locally modulate transmitter release at CBC terminals without detectably affecting the integrated membrane potential of CBCs measured in ERGs. This would explain that in the present study no effect on CBCs was detected, whereas Nemargut et al (2009) could detect a BK channel-dependent modulation when recording directly from ganglion cells. Furthermore, it is possible that bipolar cell terminal morphology plays a role in this as well: RBCs are electronically more compact than CBCs, which possess highly branched terminal systems with thin interconnecting neurites (Wässle, 2004).…”

“…We found that BK channels modulate the activity of RBCs but not the activity of CBCs and photoreceptors. To date, the function of BK channels in mammalian retina was investigated in in vitro preparations, such as vertical slices or whole mounts, in combination with pharmacological blockade of BK channels (Grimes et al, 2009;Nemargut et al, 2009). Our approach of studying BK channel function using ERG recordings in the in vivo mouse model with a genetic BK channel ablation offered two main advantages over in vitro methods: First, in the in vivo approach nonreversible bleaching of photopigments was prevented due to an intact pigment epithelium promoting recovery of photopigments.…”

“…Pharmacological blockade of BK channels reduces lightevoked excitatory input signals to ganglion cells in the lightadapted mouse retina (Nemargut et al, 2009), indicating that BK channels act presynaptic to ganglion cells, possibly at CBCs. It cannot be excluded that BK channels locally modulate transmitter release at CBC terminals without detectably affecting the integrated membrane potential of CBCs measured in ERGs.…”

“…Whether BK channels are generally expressed in cells of the mammalian cone pathway [e.g., cone bipolar cells (CBCs)] is unclear. Nevertheless, blocking BK channels reduces light-evoked input from bipolar cells and amacrine cells to ganglion cells in the lightadapted mouse retina indirectly suggesting a ubiquitous function of BK channels in both rod and cone pathways (Nemargut et al, 2009).…”

BKCa channels as physiological regulators: a focused review

“…Work by Yagi and Macleish 111 has hinted at the absence of BK Ca channels in the cones of the primate retina. However, blocking BK Ca channels induced a reduction in light-evoked input from bipolar cells and amacrine cells to ganglions in mouse retina, 112 thus suggesting a possible existence of BK Ca channels in the cone pathway in rodents. Furthermore, genetic deletion of BK Ca channels has been shown to affect the photoreceptor and bipolar cell responses in mouse retina.…”