2009A13 What is the Frank-Starling mechanism?
Describe its relationship to excitation-contraction coupling.

 

List:

·       Intro: excitation and contraction

·       Frank-Starling mechanism

 

Intro: excitation-contraction coupling

Excitation

·  Spontaneous depolarization to threshold potential in pacemaker cells

·  Action potential spreads across myocardium

·  Depolarisation of sarcolemma and T-tubules

·  Activation of T-tubular L-Ca2+

·  Ca2+-triggered Ca2+ release from ryanodine Ca2+ channels

Contraction

·  Ca2+ binds TnC, causes tropomyosin to expose actin

·  Actin-myosin-cross-bridge cycling occurs

·  Actin and myosin slide past each other

·  Muscle shortens

 

Frank-Starling mechanism:

Definition

·  Cellular: relationship between end-diastolic sarcomere length and force of contraction

·  Global: relationship between LVEDP and stroke volume

Significance

·  Allow beat-to-beat matching of venous return and cardiac output

·  i.e. heterometric autoregulation

Mechanism

·  Intrinsic property of the heart; independent of ICF [Ca2+] or [cAMP]

·  Usual sarcomere length: 1.8 μm

·  Optimal sarcomere length: 2.2 μm -> ideal balance between:

o ↓Length -> ↑actin-myosin overlap

o ↑Length -> ↑TnC affinity for Ca2+ -> ↑actin exposure by tropomyosin

Graphical representation

·  X axis: initial sarcomere length or LVEDV/LVEDP

·  Y axis: force of contraction or SV

·  Position on curve is dependent upon venous return

·  Curve shifted upward if

o     ↑contractility

o     ↓afterload