CRH-induced Electrical Activity and Calcium Signalling in Pituitary Corticotrophs
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
Model Structure
ABSTRACT: Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist corticotropin releasing hormone (CRH). There is indirect evidence suggesting that the agonist, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca2+ channels embedded in the plasma membrane. We have previously constructed a Hodgkin-Huxley-type model of this process, which indicated that an increase in the L-type Ca2+ current is sufficient to generate repetitive action potentials (LeBeau et al. (1997). Biophys. J.73, 1263-1275). CRH is also believed to inhibit an inwardly rectifying K+ current. In this paper, we have found that a CRH-induced inhibition of the inwardly rectifying K+ current increases the model action potential firing frequency, [Ca2+]i transients and membrane excitability. This dual modulatory action of CRH on inward rectifier and voltage-gated Ca2+ channels better describes the observed CRH-induced effects. This structural alteration to the model along with parameter changes bring the model firing frequency in line with experimental data. We also show that the model exhibits experimentally observed bursting behaviour, where the depolarization spike is followed by small oscillations in the membrane potential.
The original paper reference is cited below:
CRH-induced Electrical Activity and Calcium Signalling in Pituitary Corticotrophs, Paul R. Shorten, A. Bruce Robson, Alan E. McKinnon and David J.N. Wall, 2000, Journal of Theoretical Biology, 206, 395-405. PubMed ID: 10988025
cell schematic for the model
Schematic diagram of a pituitary corticotroph cell showing the transmembrane ionic currents captured by the mathematical model. Arrows indicate ionic channels and pumps. ICa-L
represents an L-type Ca2+ current responsible for most of the Ca2+ influx during an action potential. ICa-T
is a T-type voltage-sensitive Ca2+ current. A voltage-sensitive K+ current, IK-DR
, is mainly responsible for action potential repolarisation. A Ca2+-activated K+ current, IK-Ca
, is essential for bursting behaviour. The remaining leak current, IK-IR
, represents an inwardly rectifying K+ current which helps to maintain a negative resting potential. Jeff
is a plasma membrane Ca2+-ATPase pump. Within the cytosol, significant portions of Ca2+ are bound to buffers. This is denoted by Bc.