Abstract
Purpose: :
We have previously shown that cholinergic transmission between neighboring starburst cells in the developing retina plays a critical role in generating spontaneous retinal waves. Here we investigated whether the release of ACh from a starburst cell may affect the excitability of the same cell through nicotinic auto receptors.
Methods: :
Dual whole-cell patch-clamp recordings were made in conjunction with flash photolysis from pairs of overlapping displaced starburst amacrine cells in a wholemount preparation of perinatal rabbit retina. Pharmacological agents were used to characterize the nature of synaptic inputs.
Results: :
Under dual voltage-clamp recording, stimulation of one (referred to as presynaptic) starburst cell with depolarizing voltage steps evoked postsynaptic current responses from the other starburst cell (referred to as postsynaptic) in the pair. The postsynaptic currents were nicotinic and GABAergic in nature and could be isolated by holding the postsynaptic starburst cell at -70 mV (~ECl) and +10 mV, respectively. A close inspection of the current responses in the presynaptic cell revealed synaptic-like currents riding atop a Ca-activated "tail current" after the presynaptic membrane potential was returned from +10 mV to the holding potential of -70 mV. These synaptic-like currents could be blocked completely by hexamethonium, suggesting they were mediated by nicotinic receptors. Flash photolysis of DM-nitrophen, which was included in the pipette solution, also evoked a Ca-activated current and synaptic-like currents in the same starburst cell. These synaptic-like currents were detectable at -70mV (ECl), persisted in the presence of 1 mM CdCl2, and could be blocked by hexamethonium, indicating nicotinic receptor-mediated input under the condition in which endogenous calcium-dependent transmitter release from other cells were blocked.
Conclusions: :
Starburst cells in the developing rabbit express both pre- and postsynaptic nicotinic receptors. The activation of presynaptic auto receptors may provide positive auto feedback to enhance the excitability of the cell during the generation of retinal waves.
Keywords: amacrine cells • neurotransmitters/neurotransmitter systems • acetylcholine