ミトコンドリアのCa²⁺ 緩衝機構とそのクロマフィン細胞の分泌応答へ与える影響

抄録

Chromaffin cells in the perfused rat adrenal medulla were co-loaded with Fura-2 and Rhod-2 for respectively monitoring changes in the free Ca²⁺ concentration in the cytosol, [Ca²⁺]_c and that in mitochondria, [Ca²⁺]_m. When cells were stimulated for 10s with a perfusate containing 40 mM K⁺, [Ca²⁺]_m increased to a maximum level at the end of the stimulation period and then decreased to the resting level with a time course much slower than that of the simultaneously observed [Ca²⁺]_c response. With increasing the stimulation period up to 30s, the duration of [Ca²⁺]_m response increased markedly without changing its maximum level. To perform computer simulation to reproduce such characteristics of [Ca²⁺]_m responses, mitochondrial functions including Ca²⁺ uptake by uniporter, buffering of Ca²⁺ in the matrix and Ca²⁺ extrusion by Na⁺/Ca²⁺ exchanger were additionally implemented in a previously constructed model of a chromaffin cell. In simulation, a model involving precipitation of calcium phosphate salt in the mitochondrial matrix, but not with high concentrations of a soluble Ca²⁺ buffer with various affinities, allowed to reproduce the observed characteristics of [Ca²⁺]_m responses. Rotenone, which depolarizes the mitochondrial membrane potential, was used in expectation that it may reduce the Ca²⁺ clearance by mitochondria to increase secretory responses. Such expectation was in fact demonstrated in both experiments and simulations, though the extent of increase in secretory responses by rotenone was shown to be much lesser in experiments. [Jpn J Physiol 55 Suppl:S74 (2005)]