Three native somatostatin isoforms differentially affect membrane voltage-sensitive ion currents in goldfish...

Message encoding for three isoforms of somatostatin (SS) peptides, SS-14, goldfish brain (gb)SS-28 and [Pro²]SS-14, are expressed in goldfish hypothalamus and pituitary tissues. All three native goldfish SSs are active in reducing basal and stimulated growth hormone (GH) responses in cultured goldfish pituitary cells, although with different potencies and efficacies. In the present study, we examined the effects of these three endogenous SSs on electrophysiological properties of goldfish somatotrophs and their physiological relevance. Voltage-sensitive K+ , Ca²+ and Na+ channels in identified goldfish somatotrophs in primary culture were isolated using whole-cell, amphotericin B-perforated patch-clamp techniques. None of the three SSs affected Na+ currents but all three SSs increased maximal K+ current magnitude, with SS-14 being the most effective. [Pro²]SS14 did not affect Ba²+ currents through voltage-sensitive Ca²+ channels but SS14 decreased the magnitude of early and late Ba²+ currents, whereas gbSS-28 reduced that of the late Ba²+ current. Under current-clamp conditions, SS14 and gbSS28 attenuated evoked action potential magnitudes by 34% and 18%, respectively, although [Pro²]SS14 had no effects. However, all three SSs decreased basal intracellular Ca²+ levels ([Ca²+ ](i)) and suppressed basal GH release. These data suggest that, although the ability of SS-14 and gbSS-28 to decrease basal [Ca²+](i) and GH release can be explained, at least in part, by their attenuating effects on cell excitability and current flow through voltage-sensitive Ca²+ channels, [Pro²]SS14-induced reduction in GH responses and [Ca²+](i) cannot be explained by changes in Ca²+ channel properties.