The Role of G-Proteins in the Regulation of Pacemaking Activity

Kale, S. S. ; Vieth, W. R. ; Nho, K.
Springer
Published 1999
ISSN:
1573-9686
Keywords:
G-Proteins ; Pacemaking ; Ach inhibition ; ACh diffusion ; Calmodulin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Technology
Notes:
Abstract This work is concerned with modeling the key interrelated biochemical reactions involved in initiating and inhibiting pacemaking activity in the mammalian sinoatrial node. A detailed model involving G-proteins was developed to better represent the activation pathway for adenylate cyclase. Concentration profiles of an activated G-protein complex [αTC] were established as a function of the membrane bound calcium calmodulin concentration. A previously developed model used to establish temporal profiles of cAMP was improved using the G-protein effects through the [αTC] functionality. Methods were also developed to model inhibition of G-protein by acetylcholine. Analytical solutions were developed to predict acetylcholine concentration profiles as a function of diffusion parameter and duration of acetylcholine pulses. The model was used to demonstrate suppression of cAMP by acetylcholine through G-protein pathways. It provides a basis for a tool to quantify key biochemical species during stimulation and inhibition of sinoatrial node pacemaking. A stability analysis of the model equations has potential application in studying the link between the biochemical species concentrations and abnormal effects in sinoatrial node pacemaking. © 1999 Biomedical Engineering Society. PAC99: 8710+e, 8714Ee, 8719Nn, 8719Hh, 8717Aa
Type of Medium:
Electronic Resource
URL: