Modulation of potassium current and calcium influx by somatostatin in rod bipolar cells isolated from the rabbit retina via sst(2) receptors

Somatostatin (somatotropin release-inhibiting factor, SRIF) receptor subtypes are expressed by several retinal neurons, suggesting that SRIF acts at multiple levels of the retinal circuitry, although functional data on this issue are scarce. Of the SRIF receptors, the sst(2A) isoform is expressed by rod bipolar cells (RBCs) of the rabbit retina, and in isolated RBCs we studied the role of sst, receptors in modulating both K+ current (I-K) and the intracellular free [Ca2+] ([Ca2+](i)) using both voltage-clamp and Ca2+-imaging techniques. SRIF and octreotide (a SRIF agonist that binds to sst(2) receptors) inhibited that component of I-K corresponding to the activation of large-conductance, Ca2+- and voltage-dependent K+ channels (I-BK) and reduced the K+-induced [Ca2+](i) accumulation, suggesting that SRIF effects on I-BK may have been secondary to inhibition of Ca2+ channels. Octreotide effects on I-BK or On [Ca2+](i) accumulation were prevented by RBC treatment with L-Tyr(8)-Cyanamid 154806, a novel sst(2) receptor antagonist, indicating that SRIF effects were mediated by sst(2) receptor activation. The present data indicate that SRIF may modulate the information flow through second-order retinal neurons via an action predominantly at sst(2) receptors, contribute to the proposition that SRIF be added to the growing list of retinal neuromodulators, and suggest that one of its possible roles in the retina is to regulate transmitter release from RBCs.