Effect of heptanol on heart and its mechanism Baoping Chen June25,2004
Effect of heptanol on heart and its mechanism Baoping Chen June 25, 2004
1.What is heptanol 2.Effect of heptanol on the contractile function 3.Effect of heptanol on the electrical function 4.Effect of heptanol on the infarct size in ischemic heart 5.Mechanism of these actions
1. What is heptanol ? 2. Effect of heptanol on the contractile function 3. Effect of heptanol on the electrical function 4. Effect of heptanol on the infarct size in ischemic heart 5. Mechanism of these actions
l、What is heptanol? (1)Gap junction
1、What is heptanol ? (1)Gap junction
membrane cel川1 eδnnexon membrane cell 2 connexin outside M 3 4 sarcolemma inside H2N HOOCS
l、What is heptanol? (2)Heptanol is a relatively selective gap junction uncoupler
1、What is heptanol ? (2) Heptanol is a relatively selective gap junction uncoupler
l、What is heptanol? (3)Mechanism of heptanol- induced uncoupling neu shae VConductance of the Conductance A individual channels Open probability
1、What is heptanol ? (3)Mechanism of heptanolinduced uncoupling Number of gap junction channel Conductance of the individual channels Open probability Conductance
l、What is heptanol? (3)Mechanism of heptanol- induced uncoupling----three hypotheses: An indirect action mediated by an increase in inwacellular Ca2+concentration 2)A conformational change in the cell-to-cell channel resulting either from a disordering effect of the insertion of lipid-soluble molecules into membrane bilayer 3)A direct interaction of heptanol with the channel proteion
1、What is heptanol ? (3)Mechanism of heptanolinduced uncoupling ------three hypotheses: 1) An indirect action mediated by an increase in intracellular Ca2+ concentration 2) A conformational change in the cell-to-cell channel resulting either from a disordering effect of the insertion of lipid-soluble molecules into membrane bilayer 3) A direct interaction of heptanol with the channel proteion
2.Effect of heptanol on the contractile function (1)Effect on LVDP in normal perfused heart
2. Effect of heptanol on the contractile function (1) Effect on LVDP in normal perfused heart
Fig1.a,b.Effects of introduction and withdrawal of 1.0 mM heptanol in the perfusate on LVDP (a) Heptanol(1 mM) 40 D工EE 0 2 minutes Ventricular Tachycardia () (i)Control perfusion (ii)Heptanol 1 mM (ii)3 minutes after (iv)10 minutes washout,VT after washout 20
Fig1. a, b. Effects of introduction and withdrawal of 1.0 mM heptanol in the perfusate on LVDP
Fig 2.Effects of heptanol on (a)LVDP,(b) (+dp/dt)and (c)(-dp/dt),normalized to baseline values recorded in the absence of heptanol. a 1.01■ 0.5 0.0 6 1.0 0.5 0.0 、 c -1.0 -0.5 0.0 0.001 0.01 0.1 1.0 Heptanol(mM)
Fig 2. Effects of heptanol on (a) LVDP, (b) (+dp/dt) and (c) (-dp/dt), normalized to baseline values recorded in the absence of heptanol