2009A13 What is the Frank-Starling mechanism?
Describe its relationship to 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

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