Linked Life Data

11125008

Source:http://linkedlifedata.com/resource/pubmed/id/11125008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-1-8
pubmed:abstractText
Gonadotropin-releasing hormone (GnRH) secretion from native and immortalized hypothalamic neurons is regulated by endogenous Ca(2+)-mobilizing and adenylyl cyclase (AC)-coupled receptors. Activation of both receptor types leads to an increase in action potential firing frequency and a rise in the intracellular Ca(2+) concentration ([Ca(2+)](i)) and neuropeptide secretion. The stimulatory action of Ca(2+)-mobilizing agonists on voltage-gated Ca(2+) influx is determined by depletion of the intracellular Ca(2+) pool, whereas AC agonist-stimulated Ca(2+) influx occurs independently of stored Ca(2+) and is controlled by cAMP, possibly through cyclic nucleotide-gated channels. Here, experimental records from immortalized GnRH-secreting neurons are simulated with a mathematical model to determine the requirements for generating complex membrane potential (V(m)) and [Ca(2+)](i) responses to Ca(2+)-mobilizing and AC agonists. Included in the model are three pacemaker currents: a store-operated Ca(2+) current (I(SOC)), an SK-type Ca(2+)-activated K(+) current (I(SK)), and an inward current that is modulated by cAMP and [Ca(2+)](i) (I(d)). Spontaneous electrical activity and Ca(2+) signaling in the model are predominantly controlled by I(d), which is activated by cAMP and inhibited by high [Ca(2+)](i). Depletion of the intracellular Ca(2+) pool mimics the receptor-induced activation of I(SOC) and I(SK), leading to an increase in the firing frequency and Ca(2+) influx after a transient cessation of electrical activity. However, increasing the activity of I(d) simulates the experimental response to forskolin-induced activation of AC. Analysis of the behaviors of I(SOC), I(d), and I(SK) in the model reveals the complexity in the interplay of these currents that is necessary to fully account for the experimental results.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9290-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11125008-Action Potentials, pubmed-meshheading:11125008-Adenylate Cyclase, pubmed-meshheading:11125008-Calcium Channel Blockers, pubmed-meshheading:11125008-Calcium Channels, pubmed-meshheading:11125008-Calcium Signaling, pubmed-meshheading:11125008-Cell Line, pubmed-meshheading:11125008-Cell Membrane, pubmed-meshheading:11125008-Chelating Agents, pubmed-meshheading:11125008-Computer Simulation, pubmed-meshheading:11125008-Electrophysiology, pubmed-meshheading:11125008-Enzyme Inhibitors, pubmed-meshheading:11125008-Forskolin, pubmed-meshheading:11125008-Gonadotropin-Releasing Hormone, pubmed-meshheading:11125008-Hypothalamus, pubmed-meshheading:11125008-Models, Neurological, pubmed-meshheading:11125008-Neurons, pubmed-meshheading:11125008-Patch-Clamp Techniques, pubmed-meshheading:11125008-Type C Phospholipases
pubmed:year
2000
pubmed:articleTitle
Modeling of membrane excitability in gonadotropin-releasing hormone-secreting hypothalamic neurons regulated by Ca2+-mobilizing and adenylyl cyclase-coupled receptors.
pubmed:affiliation
Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. lebeau@nih.gov.
pubmed:publicationType
Journal Article