Modeling of a chromaffin cell to simulate calcium dynamics and secretoy responses

Abstract

A chromaffin cell model to analyze Ca²⁺ dynamics and secretory responses was constructed by assembling cell functions including nicotinic excitatory synapse, voltage-gated Na⁺, K⁺ and Ca²⁺ channels, Ca²⁺-activated K+ channel, buffered Ca²⁺ diffusion, Ca²⁺-handling by ER, Ca²⁺ extrusion, fluorescent Ca2+ indicator and exocytotic secretion. Standard values of parameters were determined so as to fit basic data reported in the literature. The model was applied to simulate experimental results obtained from chromaffin cells in the perfused rat adrenal medullary tissue. Observed profiles of Ca²⁺ responses to repetitive electric stimulation (1 to 50 Hz) of splanchnic nerve terminals were adequately simulated with minor adjustments of the standard parameters. Simultaneously observed secretory responses were also approximated by simulation, provided that the calculated responses were processed with time constants to detect catecholamine in the experiments. Furthermore, the inclusion of Ca²⁺ store that comprises InsP₃ receptor/channel and Ca²⁺ pump into the model enabled us to simulate various characteristic modes of muscarine-induced Ca²⁺ transients in rat chromaffin cells in a Ca²⁺-deficient medium. The model provides a useful tool for analyzing and predicting quantitative relations in various events occurring in stimulation-secretion coupling in chromaffin cell. [Jpn J Physiol 54 Suppl:S71 (2004)]