Influence of Ca 2+ channel agonists and antagonists on the post-rest staircase

Abstract

It is now generally accepted that the post-rest staircase consists of two phases, an initial fast phase occurring over the first five to six beats followed by a slow phase which occurs over a period of minutes. In this study, the influence of Ca 2+ channel antagonists (Cd 2+ and nifedipine) and agonists (Bay K 8644 and noradrenaline) on developed tension is investigated to assess the role played by the L-type Ca 2+ current (i Ca) during post-rest recovery. The results show that, at a range of stimulus frequencies, exposure of guinea-pig papillary muscles to either Cd 2+ or nifedipine greatly reduces the fast phase of the staircase and reduces the slow phase of the staircase compared to control (both effects being more prominent at higher stimulus frequencies). Exposure of guinea-pig papillary muscles to Bay K 8644 or noradrenaline potentiated both the fast and slow phases of the staircase with greater proportionate effects observed at higher stimulus frequencies. These results suggest that i Ca plays an important role in both phases of the staircase. The first post-rest beat (the rested state contraction) proved very resistant to Ca 2+ channel blockade suggesting that i Ca plays little role in this contraction which may be the result of entry of Ca 2+ into the cell via a relatively Cd 2+ insensitive pathway, for example the Na +Ca 2+ exchanger.