Regulation of L-type Calcium Channel Current by Somatostatin in Guinea-Pig Gastric Myocytes

  • Kim, Young-Chul (Department of Physiology, Chungbuk National University College of Medicine) ;
  • Sim, Jae-Hoon (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Lee, Sang-Jin (Department of Physiology, Chungbuk National University College of Medicine) ;
  • Kang, Tong-Mook (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Kim, Sung-Joon (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Kim, Seung-Ryul (Department of Biochemistry, Chungbuk National University College of Medicine) ;
  • Youn, Sei-Jin (Department of Internal Medicine, Chungbuk National University College of Medicine) ;
  • Lee, Sang-Jeon (Department of Surgery, Chungbuk National University College of Medicine) ;
  • Xu, Wen Xie (Department of Physiology, Medical School, Shaghai Jiao Tong University) ;
  • So, In-Suk (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Kim, Ki-Whan (Department of Physiology and Biophysics, Seoul National University College of Medicine)
  • Published : 2005.04.21


To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.


  1. Arimura A, Sato H, Dupont A, Nishi N, Schally AV. Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Science 189: 1007-1009, 1975
  2. Barajas-Lopez C, Huizinga JD. Different mechanisms of contraction generation in canine colon. Am J Physiol 256: G570-G580, 1986
  3. Bauer AJ, Sanders KM. Gradient in excitation-contraction coupling in canine gastric antral circular muscle. J Physiol 369: 283-294, 1985
  4. Bell GI, Reisine T. Molecular biology of somatostatin receptors. Trends Neurol Sci 16: 34-38, 1993
  5. Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Sience 179: 77-79, 1973
  6. Chen C, Israel JM, Vincent JD. Electrophysiological responses to somatostatin of rat hypophysial cells in somatotroph-enriched primary cultures. J Physiol 408: 493-510, 1989
  7. Corleto VD, Severi C, Coy DH, Delle Fave G, Jensen RT. Colonic smooth muscle cells possess a different subtype of somatostatin receptor from gastric smooth muscle cells. Am J Physiol 272: G689-697, 1997
  8. Diez J, Tamargo J, Valenzuela C. Negative effect of somatostatin in guinea-pig atrial fibres. Br J Pharmac 86: 547-555, 1985
  9. Ertan A, Arimura A. Somatostatin and the the stomach. Dig Dis Sci 5: 13-20, 1987
  10. Gomez-Pan A, Reed JD, Albinus M, Shaw B, Hall R, Besser GM, Coy DH, Kastin AJ, Schally AV. Direct inhibition of gastric acid and pepsin secretion by growth hormone-release inhibiting hormone in cats. Lancet 1: 888-890, 1975
  11. Gu ZF, Pradhan T, Coy DH, Mantey SA, Bunnett NW, Jensen RT, Maton PN. Actions of somatostatins on gastric smooth muscle cells. Am J Phyisol 262: G432-G438, 1992
  12. Gu ZF, Corleto VD, Mantey SA, Coy DH, Maton PN, Jensen RT. Somatostatin receptor subtype 3 mediates the inhibitory action of somatostatin on gastric smooth muscle cells. Am J Phyisol 268: G739-G748, 1995
  13. Hagiwara S, Byerly L. Membrane biophysics of calcium channels. Fed Proc 40: 2220-2225, 1981
  14. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved pathch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pflugers Arch-Eur J Physiol 391: 85-100, 1981
  15. Hill B. G protein-coupled mechanisms and nervous signaling. Neuron 9: 187-195, 1992
  16. Holz GG, Rane SG, Dunlap K. GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. Nature 319: 670-672, 1986
  17. Huizinga, JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A. W/kit gene required for intestinal pacemaker activity. Nature 373: 347-349, 1995
  18. Ikeda SR, Schofield GG. Somatostatin blocks a calcium current in rat sympathetic ganglion neurons. J Physiol 409: 221-240, 1989
  19. Isenberg G, Klockner U. Calcium tolerant ventricular myocytes prepared by pe-incubation in a K-B-medium. Pflugers Arch- Eur J Physiol 424: 431-438, 1982
  20. Ishikawa S, Komori K, Nagao T, Suzuki H. Effects of dilitiazem on electrical responses evoked spontaneously or by electrical stimulation in the antrum smooth muscle cells of the guinea-pig stomach. Br J Pharmacol 86: 789-797, 1985
  21. Kamimura N, Suga S, Wada J, Mio Y, Suzuki T, Wakui M. Excitatory and inhibitory actions of norepinephrine on the $Ba^{2+}$ current through L-type $Ca^{2+}$ channels of smooth muscle cells of guinea-pig vas deferens. J Cell Physiol 169: 373-379, 1996<373::AID-JCP17>3.0.CO;2-A
  22. Katzka DA, Morad M. Properties of calcium channels in guinea-pig gastric myocytes. J Physiol 413: 175-197, 1989
  23. Kim SJ, Ahn SC, Kim JK, Kim YC, So I, Kim KW. Changes in intracellular $Ca^{2+}$ concentration induced by L-type $Ca^{2+}$ channel current in guinea-pig gastric myocytes. Am J Physiol 8273: C1947-1956, 1997
  24. Kim YC, Koh SD, Sanders KM. Voltage-dependent inward currents of interstitial cells of Cajal from murine colon and small intestine. J Physiol 541(Pt 3): 797-810, 2002
  25. Kito Y, Suzuki H. Properties of pacemaker potentials recorded from myenteric interstitial cells of Cajal distributed in the mouse small intestine. J Physiol 553(Pt 3): 803-818, 2003
  26. Koh SD, Sanders KM. Modulation of $Ca^{2+}$ current in canine colonic myocytes by cyclic nucleotide-dependent mechanisms. Am J Physiol 271: C794-C803, 1996
  27. Lewis DL, Weight FF, Luini A. A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium current by somatostatin in a pituitary cell line. Proc Natl Acad Sci 83: 9035-9039, 1986
  28. Meriney SD, Gray DB, Pilar GR. Somatostatin-induced inhibition of neuronal $Ca^{2+}$ current modulated by cGMP-dependent protein kinase. Nature 369: 336-339, 1995
  29. Messenger JP. Immunohistochemical analysis of neurons and their projections in the proximal colon of the guinea-pig. Arch Histol Cytol 56: 459-473, 1993
  30. Mihara S, North RA, Surprenant A. Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones. J Physiol 390: 335-355, 1987b
  31. Mueller AL, Kunkel DD, Schwartzkroin PA. Electrophysiological actions of somatostatin (SRIF) in hippocampus: an in vitro study. Cell Mol Neurobiol 6: 363-379, 1986
  32. Ohmura T, Nishio M, Kigoshi S, Muramatsu I. Somatostatin decreases the calcium inward current in guinea-pig atria. Br J Pharmacol 99: 587-591, 1990
  33. Pittman QJ, Siggins GR. Somatostatin hyperpolarizes hippocampal pyramidal cells in vitro. Brain Res 221: 402-408, 1991
  34. Poitras P, Steinbach JH, Vandeventer G, Code CF, Walsh JH. Motilin-independent ectopic fronts of the interdigestive myoelectri complex in dog. Am J Physiol 239: 215-220, 1980
  35. Raynor K, O'Carroll AM, Kong H, Yasuda K, Mahan LC, Bell GI, Reisine T. Characterization of cloned somatostatin receptors SSTR4 and SSTR5. Mol Pharmacol 44: 385-392, 1993
  36. Ruiz E, Padilla E, Tejerina T. Effect of somatostatin on rabbit coronary arteries. Jpn J Pharmacol 90: 51-58, 2002
  37. Sanders KM, Smith TK. Motoneurones of the submucous plexus regulate electrical activity of the circular muscle of the canine proximal colon. J Physiol 380: 293-310, 1986
  38. Seki T, Yokoshiki H, Sunagawa M, Nakamura M, Sperelakis N. Angiotensin II stimulation of $Ca^{2+}$ current in vascular smooth muscle cells is inhibited by lavendustin- A and LY-294002. Pflugers Arch 437: 317-323, 1999
  39. Teitelbaum DH, O'Doriso TM, Perkins WE, Gaginella S. Somatostatin modulation of peptide-induced acetylcholine release in guinea-pig ileum. Am J Physiol 246: G509-G514, 1984
  40. Thor P, Krol R, Konturek SJ, Coy DH, Schally AV. Effect of somatostatin on myoelectrical activity of small bowel. Am J Physiol 235: E249-E254, 1978
  41. Wade GR, Barbera J, Sims SM. Cholinergic inhibition of $Ca^{2+}$ current in guinea-pig gastric and tracheal smooth muscle cells. J Physiol 491: 307-319, 1996
  42. Ward SM, Bums AJ, Torihashi S, Sanders KM. Mutation of the proto-oncogene c-kit development of interstitial cells and electrcal rhythmicity in murine intestine. J Physiol 480: 91-97, 1994
  43. Ward SM, Dixon RE, De Faoite A, Sanders KM. Voltage-dependent calcium entry underlies propagation of slow waves in canine gastric antrum. J Physiol 561: 793-810, 2004
  44. Yatani A, Codina J, Brown AM, Birnbaumer L. Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science 235: 207-211, 1987
  45. Xiong Z, Sperelakis N, Fenoglio-Preiser C. Regulation of L-type calcium channels by cyclic nucleotides and phosphorylation in smooth muscle cells from rabbit portal vein. J Vasc Res 31: 271-279, 1994
  46. Xu WX, Kim SJ, Kim SJ, So I, Kang TM, Rhee JC, Kim KW. Effect of stretch on calcium channel currents recorded from the antral circular myocytes of guinea-pig stomach. Pflugers Arch-Eur J Physiol 432: 159-164, 1996