1. Topic 16: Cardiac Muscle Properties
Structural
tissue
cellular
molecular
Functional
electrophysiological
mechanical
Experimental
2-Mar-1999:
This filled the time very comfortably; could even have added a little more. It was very hastily put together and could do with some polishing and filling out in places especially regarding the testing (Ming's thesis?). It was based on this original outline:
Cardiac Muscle mechanics:
-Differences between cardiac and skeletal muscle
-structural
cell geometry
mitochondria
myosin isoforms
regulatory proteins
titin
cell-cell connections: intercalated disks
branching fiber/sheet architecture
-functional
functional syncytium (action potential propagation)
cardiac action potential plateau - refractoriness
can not be
tetanized
spontaneous rhythmicity
pacemaker activity
higher resting tension can not be stretched as much
no descending limb
-experimental
difficult to test
requires sophisticated preparations and techniques
standard preparations:
isolated papillary muscle (nonuniform) Sara
isolated trabeculae (Henk)
techniques: spots
laser diffraction (grating equation)
see Ming's thesis
previously throught to have higher SE, tethering
effects
Cardiac Muscle uniaxial data
isometric
length dependendent activation
isotonic quick release (ter Keurs)
Hill's equation fit (Julius)
shortening deactivation (ter Keurs, Julius)
tension recovery
calcium transient (Julius)
Calcium handling in the cell (Markus Meyer/Bers)

2. Myocytes
Rod-shaped
Striated
m long
15-25 m diameter

3. Myocyte Connections
Myocytes connect to an average of 11 other cells (half end-to-end and half side-to-side)
Functional syncytium
Myocytes branch (about 12-15º)
Intercalated disks
gap junctions
connexons
connexins

4. Muscle Fiber Architecture
Muscle Band
Torrent-Guasp, 1995
Streeter et al. (1969)
endocardium
midwall
epicardium
Continuum

5. Laminar Sheet Structure
x1050
x510
x145

6. Cleavage Planes Circumferential-Radial sections
Longitudinal-Radial sections

7. Cleavage Planes are Produced by Sheets

8. Myocyte Ultrastructure
Sarcolemma
Mitochondria (M) ~30%
Nucleus (N)
Myofibrils (MF)
Sarcoplasmic Reticulum and T-tubule network

9. Cardiac Myofilaments Slow cardiac myosin isoforms Cardiac troponin
Titin

10. Cardiac Action Potential
Plateau phase 2
Refractory period
absolute
relative
Calcium current
Cardiac muscle can not be tetanized

11. Excitation-Contraction Coupling
Calcium-induced calcium release
Calcium current
Na+/Ca2+ exchange
Sarcolemmal Ca2+ pump
SR Ca2+ ATP-dependent pump
 Click image to view animation of calcium cycling

12. Muscle testing Tissue preparation right ventricular muscle
isolated rat trabecula
4000x200x90 mm
Force transducers
piezoresistive 1 V/mN
capacitive 0.1 V/mN
Displacement
variable mutual inductance transducer
Sarcomere length, L
1 mW He-Ne laser (l = 632 nm)
L = kl/d
Diffraction spacing, d
linear photodiode array
lateral effect photodetector

13. Cardiac Muscle Testing
Cardiac muscle is much more difficult to test than skeletal muscle:
tissue structure is complex and 3-D
long uniform preparations with tendons attached are not available
the best preparations are isolated papillary muscles (which hold atrioventricular valves closed during systole) and isolated trabeculae, which are more uniform but very small
cardiac muscle branching scatters light making laser diffraction more difficult
intact cardiac muscle can not be tetanized so it must be tested dynamically or artificially tetanized

14. Isometric testing
At constant muscle length, muscle preparation shortens in the middle at the expense of lengthening at the damaged ends

15. Isometric Testing 2.1 2.0 1.9 Sarcomere length, mm Sarcomere isometric
Muscle isometric
2.0
Tension, mN
time, msec
200
100
300
500
700
600
400
1.0

16. Isometric Length-Tension Curve
Peak developed isometric twitch tension (total-passive)
High calcium
Low calcium
sarcomere isometric
muscle isometric
Passive

17. Length-Dependent Activation
Isometric peak twitch tension in cardiac muscle continues to rise at sarcomere lengths >2 mm due to sarcomere-length dependent increase in myofilament calcium sensitivity

18. Isotonic Testing
Isovelocity release experiment conducting during a twitch
Cardiac muscle force-velocity relation corrected for viscous forces of passive cardiac muscle which reduce shortening velocity

19. Cardiac Muscle: Summary
Cardiac muscle fibers (cells) are short and rod-shaped but are connected by intercalated disks and collagen matrix into a spiral-wound laminar fibrous architecture
The cardiac sarcomere is similar to the skeletal muscle sarcomere
Cardiac muscle has a very slow twitch but it can not be tetanized because the cardiac action potential has a refractory period
Calcium is the intracellular trigger for cardiac muscle contraction
Cardiac muscle testing is much more difficult than skeletal muscle: laser diffraction has been used in trabeculae
Cardiac muscle has relatively high resting stiffness (titin?)
The cardiac muscle isometric length-tension curve has no real descending limb