Somatostatin depresses excitability in neurons of the solitary tract complex through hyperpolarization and augmentation of IM, a non-inactivating voltage-dependent outward current blocked by muscarinic agonists.
The synaptic function of somatostatin-containing fibers in the nervous system is controversial. Therefore, we used a slice preparation of the rat brain stem to test the electrophysiological effects of prosomatostatin-derived peptides on neurons of the solitary tract complex, which contains an abundance of somatostatin-containing fibers and cell bodies. Superfusion of both somatostatin-14 and somatostatin-28 (the precursor for somatostatin-14), but not somatostatin-28-(1-12) or -(1-10), predominantly inhibited spontaneous spike and subthreshold (probably synaptic) activity. In intracellular recordings, somatostatin-14 and -28 hyperpolarized most neurons in association with a slight (10-35%) but reproducible decrease in input resistance. These hyperpolarizing responses were augmented in depolarized cells and persisted in cells in which spontaneous inhibitory postsynaptic potentials became depolarizing after Cl- injection. These data suggest that somatostatin receptors regulate a K+ conductance. In voltage-clamp studies, somatostatin-28 and -14 induced a steady outward current and augmented the voltage-dependent, nonactivating outward K+ conductance (IM) shown to be blocked by activation of muscarinic cholinergic receptors. These results suggest (i) that somatostatin-containing elements in the solitary tract complex play an inhibitory role through the activation of postsynaptic permeability to potassium ions and (ii) that the same ion channel type may be coregulated by two neurotransmitter candidates, somatostatin and acetylcholine, through a reciprocal control mechanism.
D000818:Animals; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D053561:Somatostatin-28
D007473:Ion Channels; D010446:Peptide Fragments; D011976:Receptors, Muscarinic; D013004:Somatostatin; D053561:Somatostatin-28; D011188:Potassium