Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine and thapsigargin.
1. The effects of caffeine and thapsigargin on the contractile force and the action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to 10 mM) initially increased contractile force in a concentration-dependent manner. Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force, but the decrease was still positive as compared with control level. 3. Exchange to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In electrophysiologic, studies, caffeine shortened the action potential duration (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM), high [K]o shortened APD and decreased the action potential amplitude and resting potential. 5. These results suggest that in the presence of caffeine and/or thapsigargin calcium overload might not occur in the left ventricular papillary muscles of the guinea-pig heart.
Nario
K
K
Department of Pharmacology, Nara Medical University, Japan.
Satoh
H
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D019284:Thapsigargin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D011188:Potassium