Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons

The prosomatostatin-derived peptides somatostatin-14 (Som-14) and somatostatin-28 (Som-28) are believed to act as neurotransmitters in the central nervous system. To examine possible mechanisms by which these peptides induce their physiological actions in brain, the effects of Som-14 and Som-28 on voltage-dependent K⁺ currents in rat cerebral cortical neurons in culture were examined by using whole-cell patch-clamp techniques. Som-14 increased a delayed rectifier K⁺ current (I(K)) in the cortical neurons, while Som-28 reduced I(K) in the neurons, both in a concentration-dependent manner. Som-14 and Som-28 could induce opposite changes in I(K) in the same neurons. Elevating intracellular cAMP in the cortical neurons did not modify the effects of Som-14 or Som-28 on I(K), indicating that the peptides can regulate this ionic current through cAMP-independent mechanisms. Pretreatment of the neocortical cells with pertussis toxin, which inactivates inhibitory GTP-binding proteins, abolished both Som-14 and Som-28 modulation of I(K), indicating that Som-14 and Som-28 receptors are coupled to I(K) via GTP-binding proteins. These studies show that Som-14 and Som-28 can induce opposite biological effects, suggesting that Som-14 and Som-28, acting through distinct receptors, may function as different neurotransmitters or neuromodulators.