兴奋收缩耦联和心力衰竭的治疗

The molecular basis for myocardial contraction
Thin filament (Actin ,Tropomyosin, Troponin) Thick filament (Myosin) Other proteins
● He was an English medical doctor /physician, who is credited with being the first to correctly describe, in exact detail, the systemic circulation and properties of blood being pumped around the body by the heart.
CaC+a+++Ca++
Ca++
Ca+C+ a++Ca++
Ca++ Ca++
Ca++ Ca++
Ca++ Ca++
源自文库
Cardiac tissue and cells
B
(Guinea-pig ventricular cell)
Cardiac tissue
Function
• Conduct electrical waves • Contract in response to an electrical stimulus
ALEXANDER SANDOW,1952 (New York University)
Sandow A.Yale J Biol Med . 1952.25 (3): 176–201
● Cardiac excitation–contraction coupling is the process from electrical excitation of the myocyte to contraction of the heart (which propels blood out).
Avicenna(1167~1248)
"The power of locomotion is that which contracts and relaxes the muscles whereby the members and joints are moved, extended or flexed. This power reaches the limbs by way of the nerves and there are as many forms of power as there are of movement. Each muscle has its own peculiar purpose and it obeys the decree of the composite sense."
● The ubiquitous second messenger Ca2+ is essential in cardiac electrical activity and is the direct activator of the myofilaments, which cause contraction.
Bers DM. Nature, 2002, 415(6868): 198-205.
The cardiac action potential
● A notable difference between skeletal and cardiac myocytes is how each elevates the myoplasmic Ca2+ to induce contraction.
兴奋收缩耦联和心力衰竭的治疗
TOPICS
Excitation-contraction (EC) coupling
➢ Excitation ➢ Calcium Cycling ➢ Contraction
Alterations of E-C coupling in HF Inotropic agents for HF
William Harvey (1578 ~ 1657)
● We shall designate the entire sequence of reactions: excitation, inward acting link, and activation of contraction by the term excitation-contraction coupling.
Ca release Coincides with activation of the contractile machinery
Sliding Filament Theory
A.F. Huxley 1954
EM evidence for sliding filament theory
The micrograph shows myosin bound to actin
● In cardiac myocytes, the release of Ca2+ from the sarcoplasmic reticulum is induced by Ca2+ influx into the cell through voltage-gated calcium channels.
Pictorial OF Calcium Cycling
Ca++
Ca++ Ca++
Sarcolemma
Na+ Na+
Na+
L-Type Ca++
Ca++
Channel
Na+/Ca++ Exchanger
Ca++ Ca++ Ca++
Ca++
SERCA
SR CCaa+C+++Ra+y+RCa++CCaCa+aC++C++a+aC+++a++CC+ aaC++++aC+a+++ Ca++
Sarcoplasmic Reticulum(SR)
PLN and SERCA
the sites of interaction between PLN and SERCA
Sodium-calcium exchanger(NCX)
● Two-way transporter
● “forward”mode ● “reverse”mode ● Na:Ca=3:1