An enzymatic model of the growth hormone-releasing hormone oscillator incorporating neuronal synchronization
| Autor: | Gloria Shaffer Tannenbaum, S. Roy Caplan, Rose M. Johnstone |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Statistics and Probability
medicine.medical_specialty Phosphatase Kinetics Biology Growth Hormone-Releasing Hormone Models Biological Exocytosis General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Computer Simulation Axon 030304 developmental biology Feedback Physiological Neurons 0303 health sciences General Immunology and Microbiology Voltage-dependent calcium channel Applied Mathematics Gap junction General Medicine Growth hormone–releasing hormone medicine.anatomical_structure Endocrinology Modeling and Simulation Biophysics Calcium Calcium Channels Nerve Net Primer (molecular biology) General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Journal of Theoretical Biology. 264:984-989 |
| ISSN: | 0022-5193 |
| Popis: | Models of growth hormone (GH) rhythmogenesis which we and others have presented suggest that the GH pulses in the circulation are generated by a GH-releasing hormone (GHRH) oscillator with a 1 h periodicity. Here we examine the possibility that this is an intrinsic neuronal rhythm resulting from enzymatic reactions occurring in the axon terminals. A "Baselator" feedback reaction sequence can generate an hourly chemical burst of a primer (presumably a low molecular weight peptide) regulating Ca 2+ -triggered exocytosis of GHRH-loaded vesicles. Accordingly we propose that the priming species is largely immobilized by binding within the terminals. Free unbound primer is able to diffuse and is alternately phosphorylated and dephosphorylated by a kinase and a phosphatase (or undergoes a similar pair of complementary reactions). Under appropriate conditions involving feedback control of one or other of the enzymes the levels of both unreacted and reacted free primer peak sharply at hourly intervals. It is self-evident that synchronization between the packed terminals of the GHRH neurons at the median eminence is necessary to generate highly ordered in vivo pulses of GH release. Gap junctions provide a means of interterminal communication for the primer. Simulations of clusters of 4 adjacent axon terminals in a linear array were performed to assess whether and when synchrony can occur. With gap junctions closed the axons were set to be 90° out of phase, i.e. their chemical bursts were separated by 15 min. Opening the gap junctions, assuming either that only the unphosphorylated species permeates, or that both species permeate, resulted in rapid overall synchronization. The oscillatory systems undergo mutual entrainment and all peaks appeared simultaneously at an intermediate hourly interval. This result was independent of the mode of chemical feedback, whether positive or negative. Closing the gap junctions led to a gradual, but not immediate, loss of synchrony. |
| Databáze: | OpenAIRE |
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