The role of G-proteins in the regulation of pacemaking activity

This work is concerned with modeling the key interrelated biochemical react ions involved in initiating and inhibiting pacemaking activity in the mamma lian sinoatrial node. A detailed model involving G-proteins was developed t o better represent the activation pathway for adenylate cyclase. Concentrat ion profiles of an activated G-protein complex [alpha(T)C] were established as a function of the membrane bound calcium calmodulin concentration. A pr eviously developed model used to establish temporal profiles of cAMP was im proved using the G-protein effects through the [alpha(T)C] functionality. M ethods were also developed to model inhibition of G-protein by acetylcholin e. Analytical solutions were developed to predict acetylcholine concentrati on profiles as a function of diffusion Darameter and duration of acetylchol ine pulses. The model was used to demonstrate suppression of cAMP by acetyl choline through G-protein pathways. It provides a basis for a tool to quant ify 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 concentra tions and abnormal effects in sinoatrial node pacemaking. (C) 1999 Biomedic al Engineering Society. [S0090-6964(99)01006-1].