Ganong's Review of Medical Physiology, 23rd Edition

108 SECTION IIPhysiology of Nerve & Muscle Cells

of drugs that indirectly alter Ca2+ concentrations are dis-
cussed in Clinical Box 5–2.
During phases 0 to 2 and about half of phase 3 (until the
membrane potential reaches approximately –50 mV during
repolarization), cardiac muscle cannot be excited again; that
is, it is in its absolute refractory period. It remains relatively
refractory until phase 4. Therefore, tetanus of the type seen in
skeletal muscle cannot occur. Of course, tetanization of car-
diac muscle for any length of time would have lethal conse-
quences, and in this sense, the fact that cardiac muscle cannot
be tetanized is a safety feature.

ISOFORMS

Cardiac muscle is generally slow and has relatively low
ATPase activity. Its fibers are dependent on oxidative metab-
olism and hence on a continuous supply of O 2. The human
heart contains both the α and the β isoforms of the myosin
heavy chain (α MHC and β MHC). β MHC has lower myosin
ATPase activity than α MHC. Both are present in the atria,
with the α isoform predominating, whereas the β isoform pre-
dominates in the ventricle. The spatial differences in expres-
sion contribute to the well-coordinated contraction of the
heart.

FIGURE 5–16 Comparison of action potentials and contractile
response of a mammalian cardiac muscle fiber in a typical
ventricular cell. In the top-most trace, the most commonly viewed
surface action potential recording can be seen and it is broken down
into four regions: Q, R, S, and T. In the middle trace, the intracellular re-
cording of the action potential shows the quick depolarization and ex-
tended recovery. In the bottom trace, the mechanical response is
matched to the extracellular and intracellular electrical activities. Note
that in the absolute refractory period (ARP), the cardiac myocyte can-
not be excited, whereas in the relative refractory period (RRP) minimal
excitation can occur.

0 100 200 300

ms

ARP RRP

Mechanical

response

Action potential

recorded intra-

cellularly

Action potential

recorded with

surface electrode

0.5 g

Q

R

S

T

150 mV

FIGURE 5–17 Dissection of the cardiac action potential.

Top: The action potential of a cardiac muscle fiber can be broken

down into several phases: 0, depolarization; 1, initial rapid repolariza-

tion; 2, plateau phase; 3, late rapid repolarization; 4, baseline. Bottom:

Diagrammatic summary of Na+, Ca2+, and cumulative K+ currents dur-

ing the action potential. As is convention, inward currents are down-

ward, and outward currents are upward.

CLINICAL BOX 5–2

Glycolysidic Drugs & Cardiac Contractions

Oubain and other digitalis glycosides are commonly used

to treat failing hearts. These drugs have the effect of in-

creasing the strength of cardiac contractions. Although

there is discussion as to full mechanisms, a working hy-

pothesis is based on the ability of these drugs to inhibit the

Na, K ATPase in cell membranes of the cardiomyocytes. The

block of the Na, K ATPase in cardiomyocytes would result in

an increased intracellular Na+ concentration. Such an in-

crease would result in a decreased Na+ influx and hence

Ca2+ efflux via the Na+-Ca2+ exchange antiport during the

Ca2+ recovery period. The resulting intracellular Ca2+ con-

centration increase in turn increases the strength of con-

traction of the cardiac muscle. With this mechanism in

mind, these drugs can also be quite toxic. Overinhibition of

the Na, K ATPase would result in a depolarized cell that

could slow conduction, or even spontaneously activate. Al-

ternatively, overly increased Ca2+ concentration could also

have ill effects on cardiomyocyte physiology.

INa

IK

ICa

− 90

+20

0

1

0

0 200

2

3

4

mV

Time (ms)