title: Mechanism underlying rebound excitation in retinal ganglion cells.
abstract: Retinal ganglion cells (RGCs) display the phenomenon of rebound excitation, which is observed as rebound sodium action potential firing initiated at the termination of a sustained hyperpolarization below the resting membrane potential (RMP). Rebound impulse firing, in contrast to corresponding firing elicited from rest, displayed a lower net voltage threshold, shorter latency and was invariably observed as a phasic burst-like doublet of spikes. The preceding hyperpolarization leads to the recruitment of a Tetrodotoxin-insensitive depolarizing voltage overshoot, termed as the net depolarizing overshoot (NDO). Based on pharmacological sensitivities, we provide evidence that the NDO is composed of two independent but interacting components, including (1) a regenerative low threshold calcium spike (LTCS) and (2) a non-regenerative overshoot (NRO). Using voltage and current clamp recordings, we demonstrate that amphibian RGCs possess the hyperpolarization activated mixed cation channels/current, Ih, and low voltage activated (LVA) calcium channels, which underlie the generation of the NRO and LTCS respectively. At the RMP, the Ih channels are closed and the LVA calcium channels are inactivated. A hyperpolarization of sufficient magnitude and duration activates Ih and removes the inactivation of the LVA calcium channels. On termination of the hyperpolarizing influence, Ih adds an immediate depolarizing influence that boosts the generation of the LTCS. The concerted action of both conductances results in a larger amplitude and shorter latency NDO than either mechanism could achieve on its own. The NDO boosts the generation of conventional sodium spikes which are triggered on its upstroke and crest, thus eliciting rebound excitation.
authors.affiliation: Department of Neuroscience, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA. pratip70@yahoo.com
authors.forename: Pratip
authors.initials: P
authors.lastname: Mitra
authors.forename: Robert F
authors.initials: RF
authors.lastname: Miller
mesh_terms: D000557:Ambystoma; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D018408:Patch-Clamp Techniques; D012165:Retinal Ganglion Cells / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D002586:Cesium; D003035:Cobalt; D013779:Tetrodotoxin; D012964:Sodium