PMID- 8729058
OWN - NLM
STAT- MEDLINE
DCOM- 19960926
LR  - 20191210
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 28
IP  - 2
DP  - 1996 Feb
TI  - Functional coupling between sarcoplasmic reticulum and Na/Ca exchange in single 
      myocytes of guinea-pig and rat heart.
PG  - 253-64
AB  - It has been proposed that the cardiac Na/Ca exchanger is primed by high Ca2+ 
      concentrations derived from the sarcoplasmic reticulum (SR) in a recently 
      identified subsarcolemmal, "Na/Ca exchange-dependent Ca2+ compartment". We tested 
      this hypothesis by investigating the effect on Na/Ca exchange of interventions 
      affecting Ca2+ flux through SR. Experiments were performed in single, isolated 
      myocytes of guinea-pig and rat hearts loaded with Indo 1-AM and free Ca2+ 
      concentration was assessed by measuring the ratio of fluorescence at 405 and 495 
      nm wavelength. In guinea-pig 1.0 microM ryanodine (Ry), expected to increase Ca2+ 
      flux through the SR, decreased the amplitude of electrically stimulated Ca2+ 
      transients by 35% and inhibited their initial, rapid phase. Responses of these 
      cells to brief superfusions with 15 mM caffeine were inhibited which suggests 
      that 1.0 microM Ry depleted the SR Ca2+ stores. Diastolic Ca2+ concentration was 
      slightly increased, but it dropped below control during prolonged rest. Decrease 
      of the amplitude of the transients in these ryanodine-treated cells were reversed 
      by 2 x 10(-7) M thapsigargin (TG), an inhibitor of the SR Ca(2+)-ATPase, by 1.0 
      mM Ry, a blocker of the SR Ca2+ release channels and by low Na+ (50.0 mM) 
      superfusion. This suggests that the decreased transients in 1.0 microM Ry result 
      from uptake of Ca2+ by the SR and its rapid release to the subsarcolemmal (cleft) 
      space where a fraction is diverted out of the cell via Na/Ca exchange before it 
      can diffuse to the myofilaments. Removal of the SR from the pathway (addition of 
      TG on 1.0 mM Ry) or reversal of Na/Ca exchange diverts more transsarcolemmal Ca2+ 
      influx to the myofilaments and increases the Ca2+ transient. Decrease of the 
      resting Ca2+ concentration was blocked by 2 x 10(-7) M TG, 1.0 mM Ry, and by 5.0 
      mM Ni2+, a blocker of Na/Ca exchange. This result suggests that the effect of 1.0 
      microM Ry on resting Ca2+ concentration also resulted from increase of flux of 
      Ca2+ through the SR and out of the cell by Na/Ca exchange. In rat 1.0 microM Ry 
      decreased amplitude of the transients by approximately 75% but did not affect 
      their kinetics. TG and 1.0 mM Ry decreased the rate of rise of the transients and 
      greatly delayed their decay. This result suggests that normal kinetics of the 
      transients in the cells treated with 1.0 microM Ry depended on the preserved Ca2+ 
      flux through the SR. As SR was not able to retain Ca2+ in these cells, decay of 
      the transients must have depended on stimulated Na/Ca exchange. The results in 
      guinea-pig and rat taken together are compatible with the proposal that Ca2+ 
      released from the SR interacts with the cell's Na/Ca exchanger most probably 
      within the newly defined subsarcolemmal "Na/Ca exchange-dependent Ca2+ 
      compartment".
FAU - Janiak, R
AU  - Janiak R
AD  - Department of Clinical Physiology, Medical Center of Postgraduate Education, 
      Warsaw, Poland.
FAU - Lewartowski, B
AU  - Lewartowski B
FAU - Langer, G A
AU  - Langer GA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Antiporters)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (Terpenes)
RN  - 15662-33-6 (Ryanodine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7OV03QG267 (Nickel)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
SB  - IM
MH  - Animals
MH  - Antiporters/*metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cricetinae
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - In Vitro Techniques
MH  - Male
MH  - Myocardium/cytology/*metabolism
MH  - Nickel/pharmacology
MH  - Rats
MH  - Ryanodine/pharmacology
MH  - Sarcoplasmic Reticulum/*metabolism
MH  - Sodium-Calcium Exchanger
MH  - Terpenes/pharmacology
MH  - Thapsigargin
EDAT- 1996/02/01 00:00
MHDA- 1996/02/01 00:01
CRDT- 1996/02/01 00:00
PHST- 1996/02/01 00:00 [pubmed]
PHST- 1996/02/01 00:01 [medline]
PHST- 1996/02/01 00:00 [entrez]
AID - S0022-2828(96)90024-3 [pii]
AID - 10.1006/jmcc.1996.0024 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 1996 Feb;28(2):253-64. doi: 10.1006/jmcc.1996.0024.