PMID- 8981073 OWN - NLM STAT- MEDLINE DCOM- 19970401 LR - 20191210 IS - 0306-3623 (Print) IS - 0306-3623 (Linking) VI - 27 IP - 7 DP - 1996 Oct TI - Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine and thapsigargin. PG - 1227-35 AB - 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. FAU - Nario, K AU - Nario K AD - Department of Pharmacology, Nara Medical University, Japan. FAU - Satoh, H AU - Satoh H LA - eng PT - Journal Article PL - England TA - Gen Pharmacol JT - General pharmacology JID - 7602417 RN - 0 (Enzyme Inhibitors) RN - 0 (Phosphodiesterase Inhibitors) RN - 3G6A5W338E (Caffeine) RN - 67526-95-8 (Thapsigargin) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - RWP5GA015D (Potassium) SB - IM MH - Action Potentials/drug effects/physiology MH - Animals MH - Caffeine/*pharmacology MH - Calcium-Transporting ATPases/*antagonists & inhibitors MH - Electrophysiology MH - Enzyme Inhibitors/*pharmacology MH - Guinea Pigs MH - Heart/drug effects/*physiology MH - In Vitro Techniques MH - Myocardial Contraction/*drug effects MH - Papillary Muscles/drug effects MH - Phosphodiesterase Inhibitors/*pharmacology MH - Potassium/pharmacology MH - Sarcoplasmic Reticulum/drug effects/enzymology MH - Thapsigargin/*pharmacology EDAT- 1996/10/01 00:00 MHDA- 1996/10/01 00:01 CRDT- 1996/10/01 00:00 PHST- 1996/10/01 00:00 [pubmed] PHST- 1996/10/01 00:01 [medline] PHST- 1996/10/01 00:00 [entrez] AID - 0306362395021388 [pii] AID - 10.1016/0306-3623(95)02138-8 [doi] PST - ppublish SO - Gen Pharmacol. 1996 Oct;27(7):1227-35. doi: 10.1016/0306-3623(95)02138-8.