Neuropeptide inhibition of voltage-gated calcium channels mediated by mobilization of intracellular calcium

Many neurotransmitters and hormones regulate secretion from endocrine cells and neurons by modulating voltage-gated Ca2+ channels. One proposed mechanism of neurotransmitter inhibition involves protein kinase C, activated by diacylglycerol, a product of phosphatidyl-inositol inositol hydrolysis. Here we show that thyrotropin-releasing hormone (TRH), a neuropeptide that modulates hormone secretion from pituitary tumor cells, inhibits Ca2+ channels via the other limb of the phosphatidylinositol signaling system: TRH causes inositol trisphosphate-triggered Ca2+ release from intracellular organelles, thus causing Ca2(+)-dependent inactivation of Ca2+ channels. Elevation of intracellular Ca2+ concentration is coincident with the onset of TRH-induced inhibition and is necessary and sufficient for its occurrence. The inhibition is blocked by introducing Ca2+ buffers into cells and mimicked by a variety of agents that mobilize Ca2+. Treatments that suppress protein kinase C have no effect on the inhibition. Hence inactivation of Ca2+ channels occurs not only as a result of Ca2+ influx through plasma membrane channels, but also via neurotransmitter-induced Ca2+ mobilization. This phenomenon may be common but overlooked because of the routine use of Ca2+ buffers in patch-clamp electrodes.

[1]  B. Agranoff,et al.  Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues , 1987, Journal of neurochemistry.

[2]  P. Hockberger,et al.  A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation , 1989, Nature.

[3]  B. Bean,et al.  Classes of calcium channels in vertebrate cells. , 1989, Annual review of physiology.

[4]  M. Berridge,et al.  Control of secretion in anterior pituitary cells--linking ion channels, messengers and exocytosis. , 1988, The Journal of experimental biology.

[5]  Gershengorn Mc.  Role of inositol lipid second messengers in regulation of secretion: studies of thyrotropin-releasing hormone action in pituitary cells. , 1989 .

[6]  A. Brown,et al.  Rapid beta-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway. , 1989, Science.

[7]  A. Brown,et al.  Protein kinase activator 1-oleoyl-2-acetyl-sn-glycerol inhibits two types of calcium currents in GH3 cells. , 1988, The American journal of physiology.

[8]  A. K. Ritchie.  Thyrotropin‐releasing hormone stimulates a calcium‐activated potassium current in a rat anterior pituitary cell line. , 1987, The Journal of physiology.

[9]  M. Gershengorn.  Mechanism of thyrotropin releasing hormone stimulation of pituitary hormone secretion. , 1986, Annual review of physiology.

[10]  D. Kalman,et al.  The Role of Protein Phosphorylation in the Response of Dihydropyridine-Sensitive Calcium Channels to Membrane Depolarization in Mammalian Pituitary Tumor Cells , 1988 .

[11]  C. Hammond,et al.  Serotonin and cyclic GMP both induce an increase of the calcium current in the same identified molluscan neurons , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  J. Chad,et al.  Inactivation of calcium channels. , 1989, Comparative biochemistry and physiology. A, Comparative physiology.

[13]  J. Dubinsky,et al.  Dual modulation of K channels by thyrotropin-releasing hormone in clonal pituitary cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Cullen,et al.  Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Eckert,et al.  Inactivation of Ca channels. , 1984, Progress in biophysics and molecular biology.

[16]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[17]  R. Kramer,et al.  Neuropeptide modulation of single calcium and potassium channels detected with a new patch clamp configuration , 1990, Nature.

[18]  C. D. Benham.  Voltage‐gated and agonist‐mediated rises in intracellular Ca2+ in rat clonal pituitary cells (GH3) held under voltage clamp. , 1989, The Journal of physiology.

[19]  S. Ozawa,et al.  Electrophysiology of excitable endocrine cells. , 1986, Physiological reviews.

[20]  Samuel Thayer,et al.  Regulation of calcium homeostasis in sensory neurons by bradykinin , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  J. Barker,et al.  Intracellular Ca2+-dependent protein kinase C activation mimics delayed effects of thyrotropin-releasing hormone on clonal pituitary cell excitability. , 1987, Endocrinology.

[22]  R. Eckert,et al.  Voltage-activated calcium channels that must be phosphorylated to respond to membrane depolarization. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Tsien,et al.  Multiple types of neuronal calcium channels and their selective modulation , 1988, Trends in Neurosciences.

[24]  J. Vincent,et al.  Membrane effects of thyrotropin-releasing hormone and estrogen shown by intracellular recording from pituitary cells. , 1979, Science.

[25]  R. Tsien,et al.  Stimulation of protein kinase C recruits covert calcium channels in Aplysia bag cell neurons , 1987, Nature.

[26]  T. Tamaoki,et al.  Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. , 1986, Biochemical and biophysical research communications.

[27]  C. Armstrong,et al.  Properties of two types of calcium channels in clonal pituitary cells , 1986, The Journal of general physiology.

[28]  R. Horn,et al.  Muscarinic activation of ionic currents measured by a new whole-cell recording method , 1988, The Journal of general physiology.

[29]  R. Oswald,et al.  Pharmacological characterization of two calcium currents in GH3 cells. , 1988, The American journal of physiology.

[30]  D. Kalman,et al.  Calcium-dependent inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells , 1988, The Journal of general physiology.

[31]  M. Berridge,et al.  Distribution of two distinct Ca2+ -ATPase-like proteins and their relationships to the agonist-sensitive calcium store in adrenal chromaff in cells , 1989, Nature.

[32]  K. Dunlap,et al.  Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[33]  W. Meyerhof,et al.  An inward‐rectifying K+ current in clonal rat pituitary cells and its modulation by thyrotrophin‐releasing hormone. , 1990, The Journal of physiology.

[34]  P Hess,et al.  Calcium channels in vertebrate cells. , 1990, Annual review of neuroscience.

[35]  R. Ballester,et al.  Fate of immunoprecipitable protein kinase C in GH3 cells treated with phorbol 12-myristate 13-acetate. , 1985, The Journal of biological chemistry.

[36]  P. Albert,et al.  Relationship of thyrotropin-releasing hormone-induced spike and plateau phases in cytosolic free Ca2+ concentrations to hormone secretion. Selective blockade using ionomycin and nifedipine. , 1984, The Journal of biological chemistry.

[37]  J. McDonald,et al.  Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current , 1989, Neuron.

[38]  W. Schlegel,et al.  Thyrotropin-releasing hormone-induced rise in cytosolic calcium and activation of outward K+ current monitored simultaneously in individual GH3B6 pituitary cells. , 1988, The Journal of biological chemistry.

[39]  R Horn,et al.  Influence of sodium-calcium exchange on calcium current rundown and the duration of calcium-dependent chloride currents in pituitary cells, studied with whole cell and perforated patch recording , 1989, The Journal of general physiology.

[40]  J. Barker,et al.  Rundown of GH3 cell K+ conductance response to TRH following patch recording can be obviated with GH3 cell extract. , 1986, Biochemical and biophysical research communications.