PHYS- Contracting myocytes

Low resistance coupling

cardiac muscle cells are electrically coupled via gap junctions at the intercalated discs which allows for rapid propagation of APs across the myocardial

Syncytial behavior

coordinated contraction

Skeletal muscle characteristics

sarcomere

no syncytium

action potentials — spikes

neuromuscular transmission (stimulatory)

no gap junctions

T tubules at A-I junction

SR

intracellular calcium

troponin

force length relationship

mitochondria and capillary density varies

Cardiac muscle characteristics

sarcomere

functional syncytium

• intercalated discs

action potentials (plateau)

pacemaker potentials

depolarization by gap junctions

GAP JUNCTIONS

large T tubules at Z line

ventricular myocytes

SR moderate level

relies on both EC and IC Ca2+

troponin

Force-length relationship

high mitochondrial density

high capillary density

Collagen elastin matrix

connects myocytes nerve and capillary networks embedded in meshwork

Connective tissue matrix

structure- collagen structs; support passive elastic component prevents overstretching of the heart

• force transmission

• may hold vessels open during contraction counter surround pressure

intercalated discs

end to end transmission

Complex conic basis

membrane voltage gated, time dependent current

• sodium current (INa)

• funny current (If)

• Calcium current (Ica)

• potassium current (IK)

Cardiac myocyte AP, duration of contraction, and refractory period

100-250 ms

100-250 ms

250 ms

Skeletal myocyte AP, duration of contraction, and refractory period

3-5 ms

20-100 ms

2-3 ms

Phase 4 Resting

determined by the stable potassium conductance K>Na or Ca

Vm ~ 90 mV and IK1= inward rectifying K+ current

Phase 0: Sodium- Rapid depolarization

INa-Na+ channels

gNa rapid increase

some Na+ channels activated some inactivated

Phase I and II

all Na+ channels are inactivated and cannot be activated (refractory period)

Phase 0: Calcium- Rapid depolarization

ICa-L-type Ca2+ channels

INCX and NaCa Exchanger

gCa increase

CaL open

Phase 0

CaL closing

Phase 2

INCX reverses- Ca2+ removal

Phase 3

Phase 2

no change in voltage Na+

enter K+ leaves

-ends when Ca2+ channels close

Sources of calcium ions at the initiation of contraction

Sarcolemmal Ca2+ channel entry of extracellular Ca+ trigger

SR release RYR channels

Ca2+ induced Ca2+ release

Ca2+- TnC complex

Action myosin cycle

Cardiac myocyte relaxation

essentially the same as skeletal muscle focused on Ca2+ removal and repolarization

Parts of cardiac myocyte relaxation

SERCA (Ca 2+ ATPase)

removes Ca2+ from sarcoplasm; SR calsequesterin

Ca2+ dissociates form Troponin C

phosphorylated phospholamban —> facilitates relaxation (+lusitropic)

ATP—> break A-M bond

depolarize membrane; K+ efflux

Ca2+ ATPase

NA+ Ca2+ exchanger

Sarcolemma contains both

Frank Starling Law

the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction (the end diastolic volume), when all other factors remain constant

increased venous return

increased preload

increased calcium

increased force

heart intrinsic control

stretch leads to

Preload

passive tension prior to contraction

series and parallel elastic elements

After load

active force during contraction

Isometric Isovolumic

Internal shortening, no external shortening

Cardiac muscle preload

EDV or pressure

Cardiac muscle after load

ventricular pressure (force) during the contraction; ventricular wall stress

Cardiac isometric/isovolumic

pressure (force) no change in ventricular volume

Force generation

force length

length dependent calcium sensitivity

contractility

(more force at a lower Ca conc)

Force generation

activation state timing and or concentration of Ca2+

Contractility

the inotropic state of the myocardium determines force generation

all cells depolarize

dependent on calcium entery to trigger SR Ca2+ release

can change Ca+ or physical alignment

Positive Inotropic Effect (Norepi, Eli, B1) Autonomic control SYMPATHETIC

increased gCa (L type Ca2+ channels)

positive lusitropic effect (shortening/relaxation)

faster Ca2+ uptake (SERCA)

more calcium release

CONTRACTION

orce generation (working myocytes)

CONDUCTION

conduction pathways and working myocytes

AUTOMATICITY

- pacemaker function
- conduction pathways in pathology

Rapid Conduction

large cells
many gap junctions
AP – fast rate-of-rise
AP – greater amplitude
carried by Na + channels

Slow Conduction

small cells
few gap junctions
AP – slow rate-of-rise
AP – lesser amplitude
carried by Ca 2+ channels

CAM: Excitation-contraction coupling

1. Sarcolemmal Ca 2+ channel
entry of extracellular Ca 2+
“trigger”
2. SR calcium release
RYR channels
Ca 2+ -induced Ca 2+ release
3. Ca 2+ -TnC Complex
4. Actin-Myosin cycle