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Somatostatin Increases Voltage-Gated K⁺ Currents in GH3 Cells through Activation of Multiple Somatostatin Receptors

Prince Henry’s Institute of Medical Research (S.-K.Y., D.J.K., C.C.) and Department of Physiology (S.-K.Y., H.C.P., C.C.), Monash University, Melbourne 3168, Australia; and Department of Biology (A.D.B.), Seton Hall University, South Orange, New Jersey 07079

Address all correspondence and requests for reprints to: Chen Chen, M.D., Ph.D., Associate Professor of Physiology, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: chen.chen{at}phimr.monash.edu.au.

The secretion of GH by somatotropes is inhibited by somatostatin (SRIF) through five specific membrane receptors (SSTRs). SRIF increases both transient outward (I_A) and delayed rectifying (I_K) K⁺ currents. We aim to clarify the subtype(s) of SSTRs involved in K⁺ current enhancement in GH3 somatotrope cells using specific SSTR subtype agonists. Expression of all five SSTRs was confirmed in GH3 cells by RT-PCR. Nystatin-perforated patch clamp was used to record voltage-gated K⁺ currents. We first established the presence of I_A and I_K type K⁺ currents in GH3 cells using different holding potentials (–40 or –70 mV) and specific blockers (4-aminopirimidine and tetraethylammonium chloride). SRIF (200 nM) increased the amplitude of both I_A and I_K in a fully reversible manner. Various concentrations of each specific SRTR agonist were tested on K⁺ currents to find the maximal effective concentration. Activation of SSTR2 and SSTR4 by their respective agonists, L-779,976 and L-803,087 (10 nM), increased K⁺ current amplitude without preference to I_A or I_K, and abolished any further increase by SRIF. Activation of SSTR1 and SSTR5 by their respective agonists, L-797,591 or L-817,818 (10 nM), increased K⁺ current amplitude, but SRIF evoked a further increase. The SSTR3 agonist L-797,778 (10 nM) did not affect the K⁺ currents or the response to SRIF. These results indicate that SSTR1, -2, -4, and -5 may all be involved in the enhancement of K⁺ currents by SRIF but that only the activation of SSTR2 or -4 results in the full activation of K⁺ current caused by SRIF.

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