Somatostatin Peptides Produce Multiple Effects on Gating Properties of Native Cone Photoreceptor cGMP-Gated Channels That Depend on Circadian Phase and Previous Illumination

Abstract

A subpopulation of avian amacrine cells expresses somatostatin-14 (SS14) and somatostatin-28 (SS28), which provide a potential efferent limb for light-dependent regulation of photoreceptors. Here, we demonstrate that SS14 and SS28 modulate cone photoreceptor cGMPgated channels (CNGCs) through multiple mechanisms. In chicken cones cultured in constant darkness for 2 d after previous entrainment to light-dark (LD) cycles or in cells maintained in LD, application of 100 nM SS14 or 100 nM SS28 for either 15 min or 2 h caused a decrease in the sensitivity of CNGCs to cGMP during the night, at circadian time 16 (CT16)-CT20 or zeitgeber time 16 (ZT16)-ZT20. SS14 had no effect during the day (CT4 -CT8 or ZT4 -ZT8). These effects persist in cells pretreated with pertussis toxin (PTX) and, like dopamine, may work to reinforce long-term circadian fluctuations in CNGCs driven by oscillators within the photoreceptors themselves. In contrast, a 15 min exposure to SS28 caused a seemingly paradoxical increase in the sensitivity of CNGCs to cGMP during the early day (ZT4 -ZT6), but only in cones maintained in LD. This effect of SS28 desensitizes rapidly, is blocked by pretreatment with PTX, and is selectively mimicked by the cyclohexapeptide agonist MK-678. This transient response also requires activation of phospholipase C and protein kinase C. The transient response to SS28 may play a role in photoreceptor adaptation to rapid changes in ambient illumination. These data also show that photoreceptor responses to at least some peptide neurotransmitters depend on the previous history of light exposure.

The Cellular Building Blocks of Breathing

“…All SST receptor subtypes belong to GiPCRs. SST1 receptors activate inwardly rectifying K + conductance (75, 241, 255). In insulin-producing INS-1 cells SST2 and SST3 receptors suppress R-type voltage-gated Ca 2+ channels (340).…”

Circadian regulation of ion channels and their functions

“…While all five subtypes of SS receptors are expressed in mammalian retina (Cristiani et al. 2002; Thermos 2003), the chicken retina does not express SS receptor 1 (Chen et al. 2007).…”

“…Both SS‐14 and SS‐28 decrease CNGC sensitivity to cGMP at night, which is similar to the action of dopamine via the D 2 receptor and resistant to pertussis toxin. In addition, SS‐28, but not SS‐14, evokes a transient increase in CNGC affinity to cGMP only during the early part of the day in cone photoreceptors that have been exposed to light for 1–2 h. This transient effect by SS‐28 is mediated by pertussis toxin sensitive G protein‐coupled receptors and activation of phospholipase C and protein kinase C signaling cascades (Chen et al. 2007).…”

Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides

“…Channel sensitivity to cGMP is tuned by several pathways, including the action of calcium sensor proteins such as calmodulin (5)(6)(7)(8)(9), serine/threonine and tyrosine phosphorylation (10,11), extracellular matrix metalloproteinases (12,13), and changes in the concentration of plasma membrane phosphoinositides such as PIP 2 and PIP 3 (14 -16). Adjustments of CNG channel ligand affinity can contribute to photoreceptor adaptation and to paracrine and/or circadian changes in photoreceptor sensitivity (17)(18)(19).…”