PMID- 8907794
OWN - NLM
STAT- MEDLINE
DCOM- 19970313
LR  - 20191210
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 27
IP  - 3
DP  - 1996 Mar
TI  - Effects of thapsigargin and cyclopiazonic acid on intracellular calcium activity 
      in newborn rat cardiomyocytes during their development in primary culture.
PG  - 335-46
AB  - The effects of specific inhibitors of sarcoplasmic reticulum (SR) calcium ATPase, 
      thapsigargin (TG), and cyclopiazonic acid (CPA) were investigated on the resting 
      and transient levels of intracellular free calcium concentrations recorded in 
      Indo-1-loaded ventricular myocytes of newborn rat heart in primary culture. The 
      calcium transients were induced by caffeine (10 mM) or high potassium (100 mM) 
      solutions. In 2 day- as in 7-day-old cultured cells, the calcium transients 
      induced by 10 mM caffeine were blocked dose dependently by TG and CPA. The 
      dose-response curves suggest that TG was more efficient than CPA and that both 
      drugs were more efficient in 7-day- than in 2-day-old cells. The calcium 
      transients induced by 100 mM K+ were also strongly inhibited by these agents. The 
      lack of effect on sarcolemmal calcium currents, as shown by whole-cell 
      patch-clamp experiments, suggests that these drugs affect only SR function. In 
      cells exhibiting spontaneous activity, the associated calcium transients were not 
      affected by TG or CPA at the beginning of the culture (2-day-old cells) but were 
      fully blocked at the end (7-day-old cells). These results confirm that TG and CPA 
      specifically inhibit the cardiac SR Ca2+ pump without affecting the sarcolemmal 
      calcium current. Their blocking effect of the calcium transients as a function of 
      the developmental stage of neonatal cardiac cells in culture suggests an 
      increasing role of the SR in the regulation of intracellular calcium. This argues 
      for developmental changes of the SR through the differentiation and maturation of 
      newborn cardiomyocytes at the early stage of the postnatal life, leading to a 
      predominant role of the SR in excitation-contraction coupling mechanisms in adult 
      cells.
FAU - Gomez, J P
AU  - Gomez JP
AD  - Laboratory of General Physiology, Faculty of Sciences, Poitiers, France.
FAU - Potreau, D
AU  - Potreau D
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 3G6A5W338E (Caffeine)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Animals, Newborn/metabolism
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/*pharmacology
MH  - Heart/*drug effects
MH  - Indoles/*pharmacology
MH  - Myocardium/metabolism
MH  - Rats
MH  - Sarcoplasmic Reticulum/metabolism
MH  - Thapsigargin/*pharmacology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1097/00005344-199603000-00005 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1996 Mar;27(3):335-46. doi: 
      10.1097/00005344-199603000-00005.