Simultaneous measurement of changes in the membrane potential and the intracellular Ca2+ concentration caused by somatostatin in human GH-producing pituitary tumor cells.
Changes in the membrane potential and the intracellular Ca2+ concentration ([Ca2+]i) caused by somatostatin (SRIF) were simultaneously measured in human GH-producing pituitary tumor cells, by means of the nystatin-perforated whole cell clamp technique and Fura-2 AM. An application of 10(-8) M SRIF hyperpolarized the membrane and arrested Ca(2+)-dependent spontaneous action potentials. [Ca2+]i concurrently decreased during membrane hyperpolarization. When the membrane potential was clamped below the threshold for voltage-gated Ca2+ channels, [Ca2+]i decreased and SRIF did not further reduce [Ca2+]i. In cells which did not show spontaneous action potentials, SRIF hyperpolarized the membrane but it affected [Ca2+]i little. From these results it was concluded that the reduction in [Ca2+]i caused by SRIF was ascribed to the decrease in Ca2+ influx through voltage-gated channels during membrane hyperpolarization. The effect of SRIF on the voltage-gated Ca2+ channel current was also examined under the perforated whole cell clamp. SRIF (10(-8) M) inhibited the Ca2+ channel current to 80.8 +/- 15.4% (n = 5) of the control. Because SRIF-induced inhibition of the voltage-gated Ca2+ channel current was not prominent, it was considered that membrane hyperpolarization is the major cause of the reduction in [Ca2+]i in human GH-producing cells.
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
N
N
Yamashita
K
K
Takano
A
A
Teramoto
K
K
Tatakura
E
E
Ogata
D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism*; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D010902:Pituitary Gland / Q000503:physiopathology*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001464:Barium; D013004:Somatostatin; D013006:Growth Hormone; D002118:Calcium