Ionic Mechanisms Mediating Oscillatory Membrane Potentials in Wide-Field Retinal Amacrine Cells

Abstract

Particular types of amacrine cells of the vertebrate retina show oscillatory membrane potentials (OMPs) in response to light stimulation. Historically it has been thought the oscillations arose as a result of circuit properties. In a previous study we found that in some amacrine cells, the ability to oscillate was an intrinsic property of the cell. Here we characterized the ionic mechanisms responsible for the oscillations in wide-field amacrine cells (WFACs) in an effort to better understand the functional properties of the cell. The OMPs were found to be calcium (Ca2+) dependent; blocking voltage-gated Ca2+ channels eliminated the oscillations, whereas elevating extracellular Ca2+ enhanced them. Strong intracellular Ca2+ buffering (10 mM EGTA or bis-( o-aminophenoxy)- N,N,N′ ,N′-tetraacetic acid) eliminated any attenuation in the OMPs as well as a Ca2+-dependent inactivation of the voltage-gated Ca2+ channels. Pharmacological and immunohistochemical characterization revealed that WFACs express L- and N-type voltage-sensitive Ca2+ channels. Block of the L-type channels eliminated the OMPs, but ω-conotoxin GVIA did not, suggesting a different function for the N-type channels. The L-type channels in WFACs are functionally coupled to a set of calcium-dependent potassium ( K(Ca)) channels to mediate OMPs. The initiation of OMPs depended on penitrem-A-sensitive (BK) K(Ca) channels, whereas their duration is under apamin-sensitive (SK) K(Ca) channel control. The Ca2+ current is essential to evoke the OMPs and triggering the K(Ca) currents, which here act as resonant currents, enhances the resonance as an amplifying current, influences the filtering characteristics of the cell membrane, and attenuates the OMPs via CDI of the L-type Ca2+ channel.

An Intrinsic Neural Oscillator in the Degenerating Mouse Retina

“…Indeed, in wt retina, a subset of inhibitory amacrine cells have the biophysical characteristics that enable them to sustain periodic responses (Solessio et al, 2002;Vigh et al, 2003;PetitJacques et al, 2005). In this scheme, inhibitory amacrine cells modulate transmitter release at bipolar cell axon terminals via the activation of presynaptic GABA/glycine ionotropic receptors and trigger oscillatory spike activity in downstream ganglion cells (Vaithianathan and Sagdullaev, 2010;Margolis and Detwiler, 2010).…”

“…Alternately, excitation could be driven indirectly through intrinsically active inhibitory amacrine cells. Indeed a variety of amacrine cell types demonstrate intrinsic oscillatory potentials (Solessio et al, 2002;Vigh et al, 2003;Petit-Jacques et al, 2005). In this scheme, oscillations in particular inhibitory amacrine cells would modulate transmitter release at bipolar cell axon terminals via the activation of presynaptic GABA/glycine ionotropic receptors and trigger sustained spike activity in downstream ganglion cells (Margolis and Detwiler, 2010;Vaithianathan and Sagdullaev, 2010).…”

Abnormal Glycogen Storage by Retinal Neurons in Diabetes

“…44 Nevertheless, amacrine cells show degenerative changes in models of diabetic retinopathy 15,45 and have been implicated in diabetic neurophysiological dysfunction as measured by alterations in the oscillatory potentials of the electroretinogram. 46,47 Whether glycogen accumulation contributes to functional disturbance or cell death in the affected cells will require mechanistic studies with agents that can modulate the glycogen load. Importantly, pathologic glycogen storage may also be relevant to neuronal dysfunction in diabetic patients as primate retina contains a subpopulation of amacrine cells that express GyP, confirming a need for glycogen metabolism in these cells.…”

The Role of BKCa Channels in Electrical Signal Encoding in the Mammalian Auditory Periphery

“…In nonmammalian auditory hair cells, BK Ca contributes to electrical frequency tuning in the absence of APs (Art and Fettiplace, 1987;Fettiplace and Fuchs, 1999). However, less is known about the impact of BK Ca on electrical signaling in other nonspiking cells, such as retinal neurons (Sakaba et al, 1997;Mitra and Slaughter, 2002) or mechanosensory hair cells of the mammalian ear, despite strong expression of BK Ca in these cells (Skinner et al, 2003;Vigh et al, 2003). Mammalian inner hair cells (IHCs) are a useful system to study the role of BK Ca in nonregenerative electrical signaling operating in a frequency range far beyond that of usual neurons.…”