PMID- 7599337
OWN - NLM
STAT- MEDLINE
DCOM- 19950807
LR  - 20191210
IS  - 0867-5910 (Print)
IS  - 0867-5910 (Linking)
VI  - 46
IP  - 1
DP  - 1995 Mar
TI  - Thapsigargin inhibits the effects of noradrenaline and high [Ca2+]o on kinetics 
      but not on amplitude of contraction in the single myocytes of guinea-pig heart.
PG  - 45-55
AB  - We investigated the effect of selective blocker of Ca(2+)-ATPase of sarcoplasmic 
      reticulum (SR), thapsigargin (TG), on the responses of single myocytes of 
      guinea-pig heart to high [Ca2+]o and noradrenaline (NA). The cells were loaded 
      with acetomethylester of Indo 1 and free [Ca2+]i monitored as the ratio of 
      fluorescence at 405 and 495 nm. The changes in cell length were monitored by a TV 
      displacement system. In the normal cells increase in [Ca2+]o from 2.0 to 5.0 mM 
      increased amplitude of contraction by 154 +/- 8%, decreased the time to peak 
      contraction from 343 +/- 25 ms to 328 +/- 20 ms and decreased the total duration 
      of contraction from 813 +/- 81 ms to 800 +/- 47 ms (not significant). The rate of 
      rise of rapid phase of Ca2+ transients and their amplitude was increased and 
      decay accelerated. The 10(-9) mM NA increased the amplitude of contraction by 154 
      +/- 9%, decreased time to peak contraction from 343 +/- 25 ms to 273 +/- 17 ms 
      and the total duration of contraction from 813 +/- 81 ms to 603 +/- 28 ms. The 
      rate of rise of the rapid phase of Ca2+ transients was greatly accelerated and 
      their amplitude was increased. The 10(-7) M(TG) blocked completely the rapid 
      phase of Ca2+ transients, increased time to peak [Ca2+]i and delayed decay. Total 
      amplitude of the transients was hardly affected. Accordingly, time to peak 
      contraction was prolonged to 583 +/- 50 ms but the amplitude of contraction was 
      only slightly decreased. Calcium stores in the SR were completely depleted as 
      assessed by caffeine Ca2+ transients and contractures. In the cells pretreated 
      with TG 10(-9) M NA but not 5.0 mM Ca2+ increased amplitude of the transients. 
      Amplitude of contractions was increased by both agents more than in the control 
      cells. The 5.0 mM Ca2+ slightly decreased time to peak contraction and NA tended 
      to increase it. Both inotropic agents accelerated relaxation. It is concluded 
      that amplitude of contractions may be increased by stimulation of Ca2+ influx, 
      however, the control of kinetics of contraction results from altered handling of 
      the influx by the functioning SR.
FAU - Janiak, R
AU  - Janiak R
AD  - Department of Clinical Physiology, Medical Center of Postgraduate Education, 
      Warsaw, Poland.
FAU - Lewartowski, B
AU  - Lewartowski B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Poland
TA  - J Physiol Pharmacol
JT  - Journal of physiology and pharmacology : an official journal of the Polish 
      Physiological Society
JID - 9114501
RN  - 0 (Terpenes)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Calcium/*pharmacology
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Female
MH  - Guinea Pigs
MH  - Heart/*drug effects
MH  - Kinetics
MH  - Male
MH  - Myocardial Contraction/*drug effects
MH  - Myocardium/cytology
MH  - Norepinephrine/antagonists & inhibitors/*pharmacology
MH  - Osmolar Concentration
MH  - Terpenes/*pharmacology
MH  - Thapsigargin
EDAT- 1995/03/01 00:00
MHDA- 1995/03/01 00:01
CRDT- 1995/03/01 00:00
PHST- 1995/03/01 00:00 [pubmed]
PHST- 1995/03/01 00:01 [medline]
PHST- 1995/03/01 00:00 [entrez]
PST - ppublish
SO  - J Physiol Pharmacol. 1995 Mar;46(1):45-55.