Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs.

Abstract

SUMMARY1. Somatotrophs from enzymatically dispersed anterior pituitary glands of rats, enriched to > 94% purity by density gradient centrifugation, were studied within 16 h of isolation using patch clamp recording methods in the conventional whole-cell and the perforated-patch configurations.2. Rhythmic oscillations of membrane potential gave rise to action potentials in thirty-six of fifty-two cells studied with the perforated-patch technique. Membrane potential oscillated between -70 mV and -25 mV with an average frequency (mean + S.D.) of 0-9 + 0-9 S-1.3. The current-voltage (I-V) relationship of cells was linear at negative potentials with outward rectification at potentials positive to -40 mV. Evidence that the outward current was due to K+ channels came from the deactivation tail currents, which reversed direction close to the K+ equilibrium potential (EK). The reversal potential shifted 60 mV per tenfold change of external K+ concentration ([K+]o), as expected for K+ current.4. Suppression of outward current by tetraethylammonium (TEA) provided additional evidence for K+ current. Cd2+ reduced outward current, suggesting the presence of Ca2+-activated K+ conductance.5. Depolarizing commands elicited transient inward Na+ current and a sustained Ca2+ current (ICa). ICa was recorded in isolation with Cs+ and TEA in the recording pipette and 10 mM-Ba2+ as the charge carrier. Activation Of ICa began at -40 mV, with peak inward current at 0 to +10 mV. The half-inactivation potential was -35 mV. In addition, ICa was blocked by nifedipine. These characteristics indicate the presence of L-type Ca2+ channels in somatotrophs.6. Somatostatin caused hyperpolarization and suppressed the spontaneous bursts of action potentials. Under voltage clamp, somatostatin activated an inwardly rectifying current that reversed direction near EK. When EK was altered by elevation of [K+]o, the reversal potential of the somatostatin-induced current shifted 55 mV per tenfold change of [K+]o, as predicted for a K+ current by the Nernst relation.The somatostatin-induced conductance (gK) was greater at more negative potentials, and the activation range shifted positive with elevation of [K+]0.

Characterization of a Plasma Membrane Calcium Oscillator in Rat Pituitary Somatotrophs

“…In other words, these cells are quiescent, and the addition of growth hormone-releasing hormone (GHRH) is required to initiate firing. This is in contrast with the results by Sims et al (20) and Holl et al (21), who observed spontaneous firing of APs and extracellular Ca 2ϩ -dependent fluctuation in [Ca 2ϩ ] i in a fraction of somatotrophs. Several laboratories have also reported that gonadotrophs, lactotrophs, and corticotrophs exhibit periods of spontaneous firing of APs (22)(23)(24)(25).…”

Frequency-Dependent, Cell Type-Divergent Signaling in the Hippocamposeptal Projection

“…However, the GABA(B) receptor antagonist CGP 55845 hydrochloride showed no evidence of even a partial block (n ϭ 2, data not shown). HS cells also express SST (Jinno and Kosaka, 2002;Gulyás et al, 2003), a neuropeptide known to signal through GIRK channels (Mihara et al, 1987;Sims et al, 1991) and to evoke similar inhibitory responses in other brain regions (Twery and Gallagher, 1989;Greene and Mason, 1996;Schweitzer et al, 1998), so we hypothesized that the response might be due to SST released by optogenetic stimulation from HS terminals. Indeed, we were able to achieve a partial block (ϳ30%) with the nonspecific SSTR antagonist cyclosomatostatin (5 M; Fig.…”

Somatostatin‐mediated inhibitory postsynaptic potential in sympathetically denervated guinea‐pig submucosal neurones.

“…The most common neuronal action of somatostatin is one of inhibition with its most common cellular mechanism of action being a membrane hyperpolarization brought about by activation of inwardly rectifying potassium channels Inoue, Nakajima & Nakajima, 1988;Lewis & Clapham, 1989;Sims, Lussier & Kraicer, 1991) . This cellular mechanism underlies inhibitory postsynaptic potentials (IPSPs) at several muscarinic, adrenergic and y-aminobutyric acid (GABAB) synapses (Hartzell, Kuffler, Stickgold & Yoshikami, 1977;Dodd & Horn, 1983;Surprenant & North, 1988;Mihara & Nishi, 1989;Nicoll, Malenka & Kauer, 1990); somatostatin might also be expected to mediate similar IPSPs at sites where it is known to be released.…”