Influence of Ca2+ channel agonists and antagonists on the post-rest staircase.
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 Ca2+ channel antagonists (Cd2+ and nifedipine) and agonists (Bay K 8644 and noradrenaline) on developed tension is investigated to assess the role played by the L-type Ca2+ current (iCa) during post-rest recovery. The results show that, at a range of stimulus frequencies, exposure of guinea-pig papillary muscles to either Cd2+ 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 iCa plays an important role in both phases of the staircase. The first post-rest beat (the rested state contraction) proved very resistant to Ca2+ channel blockade suggesting that iCa plays little role in this contraction which may be the result of entry of Ca2+ into the cell via a relatively Cd2+ insensitive pathway, for example the Na(+)-Ca2+ exchanger.
Harrison
S
S
Department of Physiology, University of Leeds, UK.
Milner
R
R
Boyett
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D005082:Physical Exertion / Q000502:physiology*; D019831:Sodium-Calcium Exchanger
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D009638:Norepinephrine