Representative data of myocyte contraction. Myocytes that overexpress the V49A point mutation in PL display increased contractility, while myocytes that ...
Spécialité Cardiovasculaire – Hémostase - Respiration 14 novembre 2006
Couplage Excitation – Contraction Relaxation du myocyte cardiaque Pr Jean-Jacques Mercadier Départements de Physiologie et de Cardiologie et INSERM U 460 Groupe Hospitalier Bichat – C. Bernard, Paris, France
Myocarde
Appareil contractile d’une cellule musculaire Système longitudinal Réticulum sarcoplasmique Diades\Triades
Sacs latéraux Mitochondrie Attention: Triades: plutôt dans les cellules musculaires squelettique Diades: plutôt dans les cellules musculaires cardiaques
Le système tubulaire Transverse
Ouverture du tubule transverse à l’espace extra-cellulaire Sarcolèmme
Tubules transverse
Segments du réticulum sarcoplasmique
Myofibrilles
me mb ra
mm a
10-25 L-CaCh:100 RyR
SR
sar co le
L-type Ca2+ channels
ne
System of Ca2+ extrusion from the SR and coupled gating of ryanodine receptors (RyRs)
15nm CSQ
junction
Free Ca2+
Ca2+
CSQ
Bound Ca2+
CSQ
(Calsequestrin)
TT
cytosol FKBP12.6 RyR2
« CICR »
RS
Bers 2004, JMCC Coupled gating of RyRs: synchronous opening and closure of all RyRs located in a couplon: major role of FKBP12.6 (Calstabin 2)
Cardiac intracellular calcium release channels Marks AR, Circ Res 2000;87:8-11
Excitation – contraction – relaxation of cardiac myocytes sarcolemma
Ca
2+
CSQ
Ca2+
FKBP 12.6 L-type Ca2+ channel
• Calreticulin • Histidine-rich Ca2+ BP
SR
RyR2
Ca2+
Ca2+
Ca2+
2+ SERCA2a Ca
1
PL
Troponin C
P
Ca2+ 3
4
2
PMCA
Na+ NCX
Mitochondria
Figure 4. Inhibition of the interaction between PLB and SERCA2a activates cardiac contractility
Representative data of myocyte contraction. Myocytes that overexpress the V49A point mutation in PL display increased contractility, while myocytes that overexpress the wild-type PLB exhibit decreased contractility when compared to noninfected myocytes
Minamisawa et al. Cell 1999; 99:313-322
β-adrenergic signal transduction
β1 and β2-
Cholinergic receptor
adrenergic receptors
M2
Gs + AC _ Gi ATP cAMP
PKA
contraction relaxation
Augmentation de la contraction et de la relaxation lors de la stimulation ß adrénergique du myocyte cardiaque
Signal Calcique 2
200
1
-0.2
ICa-L 1 150
-0.6
∆[Ca]i nM
( nA )
100
HP=-60mV TP= 0mV
-1
50
-1.4 2
1-Control 2-1µM Isoproterenol (β+)
0
200
400
600
800
SERCA and its regulation by phospholamban 1
P
P P 20 30
52
SR MacLennan, Nature Reviews 2003
Ca2+ cycling during hypertrophy and failure sarcolemma SR
FKBP 12.6
Ca
CSQ
2+
Ca2+ L-type Ca channel
ICa
Ca2+ leak RyR2
Ca2+
SERCA2a
2+
1
Ca2+ P
PL Troponin C Ca2+ 3
4
2
PMCA ? NCX Pogwizd et al., Circ. Res. 2001
Mitochondria
ALTERATION OF THE CALCIUM TRANSIENT IN FAILING HUMAN CARDIAC MYOCYTES
INSERM U 698 Faculté X. Bichat
Beuckelmann et al. Circulation 1992
Phospholamban phosphorylation during HF
P. Rodriguez & E.G. Kranias Arch. Mal. Cœur, in press
Phospholamban phosphorylation during HF
P. Rodriguez & E.G. Kranias Arch. Mal. Cœur, in press
Hypothesis sarcolemma NCX
PMCA
P
cytosol
CaMKII vsPP1
CaMKII P
P
SERCA CSQ
DHPR
leak
Free [Ca2+]SR P CSQ
Ca2+
INa/Ca
NCX
+
P 3Na+
SR
PLB
TnI
P
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