Inhibitory effect of somatostatin-14 on L-type voltage-gated calcium channels in cultured cone photoreceptors requires intracellular calcium.
The inhibitory effects of somatostatin have been well documented for many physiological processes. The action of somatostatin is through G-protein-coupled receptor-mediated second-messenger signaling, which in turn affects other downstream targets including ion channels. In the retina, somatostatin is released from a specific class of amacrine cells. Here we report that there was a circadian phase-dependent effect of somatostatin-14 (SS14) on the L-type voltage-gated calcium channels (L-VGCCs) in cultured chicken cone photoreceptors, and our study reveals that this process is dependent on intracellular calcium stores. Application of 500 nM SS14 for 2 h caused a decrease in L-VGCC currents only during the subjective night but not the subjective day. We then explored the cellular mechanisms underlying the circadian phase-dependent effect of SS14. The inhibitory effect of SS14 on L-VGCCs was mediated through the pertussis-toxin-sensitive G-protein-dependent somatostatin receptor 2 (sst2). Activation of sst2 by SS14 further activated downstream signaling involving phospholipase C and intracellular calcium stores. Mobilization of intracellular Ca2+ was required for somatostatin induced inhibition of photoreceptor L-VGCCs, suggesting that somatostatin plays an important role in the modulation of photoreceptor physiology.
Jian
Kuihuan
K
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX 77843-4458, USA.
Barhoumi
Rola
R
Ko
Michael L
ML
Ko
Gladys Y-P
GY
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D002940:Circadian Rhythm / Q000502:physiology; D003484:Cyanamide / Q000378:metabolism; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010456:Peptides, Cyclic / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D006728:Hormones; D010456:Peptides, Cyclic; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D003484:Cyanamide; D013004:Somatostatin; D004533:Egtazic Acid; C040968:seglitide; D037342:Pertussis Toxin; D002118:Calcium