Regulation of Gap Junctional Coupling in Photoreceptors (pp. 97-112)
Authors: (Hongyan Li, John O’Brien, The Richard S. Ruiz, M.D. Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Texas, USA)
Abstract: Cone photoreceptors are well coupled to each other and to rods through connexin 36 (Cx36) gap junctions. This coupling is an essential part of photoreceptor physiology, suppressing voltage noise, improving the fidelity of the output synapses, and providing a route through which rod signals enter the cone pathway to code increases in light intensity as rod synapses reach saturation. Coupling is substantially reduced in the daytime to optimize the retina for bright light, cone-mediated vision. The plasticity of photoreceptor gap junctional coupling is controlled both by light/dark adaptation and by a circadian rhythm. Rod-cone coupling is reduced in the subjective day and increased in subjective night. Dopamine has long been implicated in the light-driven reduction in coupling and a circadian rhythm of dopamine secretion can account for the reduction of coupling in subjective day. In photoreceptors, dopamine acts through a receptor with D2-like pharmacology, demonstrated to be the D4 receptor in mouse. Activation of this receptor inhibits adenylyl cyclase (AC) and reduces intracellular cAMP.
Recent studies have shown that Cx36 phosphorylation controls photoreceptor coupling and is in turn regulated by cAMP-dependent protein kinase (PKA) activity. The well-known dopamine signaling pathway suppressing the activity of PKA can explain the uncoupling of photoreceptor gap junctions in the daytime. However, evidence suggests that additional signaling may impose the nighttime state. An emerging candidate for the
nighttime or dark signal is extracellular adenosine. Adenosine receptor agonists drive increased phosphorylation of Cx36 in photoreceptors and increased photoreceptor coupling. The pathway involves an A2a adenosine receptor and increased PKA activity. Thus dopamine and adenosine receptor activity may co-regulate photoreceptor coupling through opposing actions on a common signaling pathway leading to PKA activity and gap junction phosphorylation. This arrangement establishes a push-pull signal cascade to tightly control photoreceptor coupling, with adenosine serving as a darkness/night signal and dopamine serving as a light/daytime signal.
Open Access item.
Click below PDF icon for free download.
This is an Open Access item. Click above PDF icon for free download.