PMID- 8203582
OWN - NLM
STAT- MEDLINE
DCOM- 19940705
LR  - 20191210
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 266
IP  - 5 Pt 2
DP  - 1994 May
TI  - Effects of thapsigargin in normal and pretreated with ryanodine guinea pig 
      cardiomyocytes.
PG  - H1829-39
AB  - We compared the effects of thapsigargin (TG), a selective blocker of 
      Ca(2+)-adenosinetriphosphatase of sarcoplasmic reticulum (SR), and ryanodine (Ry) 
      in the single isolated myocytes of guinea pig ventricular myocardium loaded with 
      indo 1 acetoxymethyl ester (AM). TG (2 x 10(-7) M) inhibited the rapid phase of 
      Ca2+ transient, increased time to peak intracellular Ca2+ concentration ([Ca2+]i) 
      from 158 +/- 12 to 391 +/- 60 ms and decreased the total amplitude of the 
      transient to 89 +/- 4% of the pre-TG control. Time to peak of contractions 
      increased from 350 +/- 47 to 410 +/- 37 ms and total duration from 666 +/- 62 to 
      850 +/- 198 ms. Total amplitude of contractions was hardly affected. In the cells 
      not loaded with indo 1-AM TG decreased the amplitude of contractions to 71 +/- 3% 
      of control. When the effects of TG were fully developed, the cells ceased to 
      respond to 1 s of superfusion with 15.0 mM caffeine with transient elevation of 
      [Ca2+]i and/or transient contracture. TG did not affect the amplitude or time 
      course of Ca2+ current (ICa) or the current-voltage relation. We propose that 
      Ca2+ transients and contractions in the cells treated with TG were initiated by 
      sarcolemmal Ca2+ influx. Ry (1.0 microM) initiated similar changes in the time 
      course of Ca2+ transients and contractions as TG; however, total amplitude of the 
      transients and contractions was reduced to 78 +/- 5 and 55 +/- 7% of the control, 
      respectively. The SR Ca2+ was also depleted by Ry. TG superfused over the cells 
      pretreated with Ry increased the amplitude of Ca2+ transients and respective 
      contractions to the pre-Ry level. TG did not affect the ICa in the cells 
      pretreated with Ry nor did it change configuration of action potentials to 
      increase the Ca2+ influx. We propose that the effect of Ry on amplitude of Ca2+ 
      transients and contractions results from the trapping of a fraction of 
      sarcolemmal Ca2+ influx by the SR and its rapid release into subsarcolemmal 
      space. From there it is extruded out of the cell by Na(+)-Ca2+ exchange before 
      ever reaching the contractile system.
FAU - Lewartowski, B
AU  - Lewartowski B
AD  - Department of Clinical Physiology, Medical Center of Postgraduate Education, 
      Warsaw, Poland.
FAU - Rozycka, M
AU  - Rozycka M
FAU - Janiak, R
AU  - Janiak R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Chelating Agents)
RN  - 0 (Indoles)
RN  - 0 (Terpenes)
RN  - 112926-02-0 (Indo-1 pentaacetoxymethyl ester)
RN  - 15662-33-6 (Ryanodine)
RN  - 3G6A5W338E (Caffeine)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Action Potentials/drug effects/physiology
MH  - Animals
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - Chelating Agents
MH  - Electric Stimulation
MH  - Female
MH  - Guinea Pigs
MH  - Heart/drug effects/*physiology
MH  - In Vitro Techniques
MH  - Indoles
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Myocardial Contraction/drug effects/*physiology
MH  - Myocardium/metabolism
MH  - Ryanodine/*pharmacology
MH  - Terpenes/*pharmacology
MH  - Thapsigargin
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
AID - 10.1152/ajpheart.1994.266.5.H1829 [doi]
PST - ppublish
SO  - Am J Physiol. 1994 May;266(5 Pt 2):H1829-39. doi: 
      10.1152/ajpheart.1994.266.5.H1829.