The role of G-proteins in the regulation of pacemaking activity.
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 [alpha(T)C] 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 [alpha(T)C] 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.
Kale
S S
SS
Consulting Chemical Engineer, Houston, TX, USA.
Vieth
W R
WR
Nho
K
K
D000109:Acetylcholine / Q000737:chemistry / Q000502:physiology*; D000262:Adenylyl Cyclases / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D002147:Calmodulin / Q000737:chemistry / Q000502:physiology*; D000242:Cyclic AMP / Q000737:chemistry / Q000502:physiology*; D004058:Diffusion; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006868:Hydrolysis; D008322:Mammals; D008955:Models, Cardiovascular; D008956:Models, Chemical; D009716:Numerical Analysis, Computer-Assisted; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000502:physiology*; D012849:Sinoatrial Node / Q000502:physiology*
D002147:Calmodulin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000109:Acetylcholine