PMID- 7585826 OWN - NLM STAT- MEDLINE DCOM- 19951226 LR - 20191210 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 30 IP - 3 DP - 1995 Sep TI - Effects of thapsigargin on aequorin-injected and skinned preparations of ferret ventricular muscles. PG - 357-62 AB - OBJECTIVE: We investigated the effects of thapsigargin (TG) (0.1-1 microM) on the relation between intracellular Ca2+ concentration and tension in ferret papillary muscles using aequorin-injected and skinned preparations. METHODS: Aequorin was injected into the superficial cells of ferret papillary muscles; the Ca2+ signals of aequorin and tension in twitch and those with the application of 15 mM caffeine were simultaneously measured. The alteration of Ca2+ sensitivity of the contractile elements was examined by measuring the pCa-tension relation in Triton-X-treated skinned preparations. RESULTS: TG decreased the peak of the Ca2+ signal accompanied by a prolonged decay time. However, the tension was scarcely altered even at 1 microM TG. TG inhibited the caffeine-induced Ca2+ signal. Prolongation of decay of the Ca2+ signal by TG in twitch was further enhanced by isoprenaline (10 nM). The pCa-tension relation of the skinned preparation was slightly but significantly shifted to the right by TG. CONCLUSIONS: The apparent dissociation of the effects of TG on the Ca2+ signal and tension in intact preparations is not a result of alteration of the Ca2+ sensitivity of the myofilaments. The effects of TG in multicellular preparations are probably limited to the outer layer of the preparation. The slower time course of the Ca2+ signal induced by TG is due to the inhibition of Ca2+ uptake by sarcoplasmic reticulum, which is more significantly observed when the intracellular Ca2+ transient is increased by isoprenaline. FAU - Tanaka, T AU - Tanaka T AD - Department of Physiology, Jikei University School of Medicine, Tokyo, Japan. FAU - Komukai, K AU - Komukai K FAU - Kawai, M AU - Kawai M FAU - Tanaka, E AU - Tanaka E FAU - Kurihara, S AU - Kurihara S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Cardiotonic Agents) RN - 0 (Terpenes) RN - 3G6A5W338E (Caffeine) RN - 50934-79-7 (Aequorin) RN - 67526-95-8 (Thapsigargin) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - L628TT009W (Isoproterenol) RN - SY7Q814VUP (Calcium) SB - IM MH - Aequorin/*pharmacology MH - Animals MH - Caffeine/pharmacology MH - Calcium/metabolism MH - Calcium-Transporting ATPases/*antagonists & inhibitors MH - Cardiotonic Agents/pharmacology MH - Ferrets MH - In Vitro Techniques MH - Isoproterenol/pharmacology MH - Papillary Muscles/*drug effects/metabolism MH - Sarcoplasmic Reticulum/drug effects/metabolism MH - Terpenes/*pharmacology MH - Thapsigargin EDAT- 1995/09/01 00:00 MHDA- 1995/09/01 00:01 CRDT- 1995/09/01 00:00 PHST- 1995/09/01 00:00 [pubmed] PHST- 1995/09/01 00:01 [medline] PHST- 1995/09/01 00:00 [entrez] AID - 0008-6363(95)00053-4 [pii] PST - ppublish SO - Cardiovasc Res. 1995 Sep;30(3):357-62.