BIOL4510 / KINE4510
The purpose of electrical depolarization (i.e. action potentials) is to initiate contraction. This
process is called excitation-contraction coupling (E-C coupling). The2+lectrical changes in the
muscle cell (myocyte) induce an increase in intracellular Ca leading to the development of
contraction. Muscle relaxation ensues following a decrease in intracellular Ca . There are 2+
significant differences in E-C coupling in skeletal, cardiac and smooth muscle.
Top figure showing action potentials (APs) in Cardiac Muscle vs Skeletal Muscle. In sk muscle APs are
very short (3-5msecs) and a single AP generates a twitch force lasting 50-100 msecs. In cardiac
muscle APs are much longer (~200msecs) and a single AP generates a twitch force lasting ~300
msecs. Bottom figure shows that APs in sk muscle have a rapid recovery time (short refractory time) and
therefore sk muscle can be rapidly and repetitively stimulated which causes fusion of twitches and the
generation of tetanus. In fact, sk muscle contraction usually involves tetanization of individual motor
units. Cardiac muscle has long AP relative to force/pressure generation. Therefore, tetanization is not
possible. Cardiac muscle cannot be stimulated faster than the refractory period of the AP.
Note: refractory period ~ AP duration since electrical (and thus mechanical stimulation of muscle) can
only occur if most Na channels are available to initiate and propagate APs. Therefore refractory period
controlled by rate of recovery of Na channels from inactivation (which requires membrane
repolarization). Thus, long APs in cardiac muscle prevent tetanization of cardiac muscle. Why is this a
critical feature of heart?
1 E-C Coupling in the Heart
AP generation occurs in order to induce muscle contraction. The process of membrane
depolarization leading to muscle contraction is called excitation-contraction coupling = ECC =
the events underlying the mechanical response (muscle contraction) to an electrical
depolarization (action potential). In the heart, ECC is dependent on a rise in Ca which
catalyzes the conversion of ATP into force and mechanical work by myosin and the contractile
proteins. The Ca 2+originates from both intracellular (sarcoplasmic reticular) and extracellular
shows the absence of contraction when extracellular Ca 2+ is removed. Note: Sk,. Muscle will
still contract in the absence of extracellular Ca2+
It has been calculated that there is an increase of 90 120 M total Ca in the cytoplasm with
each cardiac contraction. The rise in free [Ca ] which is about 1M. The free Ca 2+rise is the
tip-of-the=iceberg. The low free [Ca ] is the result of buffering (100:1) of Ca 2+by intracellular
proteins. The major buffers being troponin-C (~150M) and calmodulin (~20M).as well as
2 - Ca 2+ transients (i.e. the transient rise in Ca2+associated with ECC) is typically measured
with fluorescent indicators which are molecules that bind Ca and thereby change their
flevel of fluorescence. Recent Nobel Prize awarded to Roger Tsien who developed many
of these dyes.
Photo: U. Montan
Osamu Shimomura Martin Chalfie Roger Y. Tsien
The Nobel Prize in Chemistry 2008 was awarded jointly to Osamu Shimomura, Martin Chalfie and Roger Y. Tsien "for the
discovery and development of the green fluorescent protein, GFP".
- these dyes have a number of carboxylic acid moieties that bind Ca plus a large pi-bond
structure that provides a structure for resonating electrons over a relative continuous range of
frequencies corresponding to visible light. This allows Ca 2+imagining to be performed.
3 The major car2+ac cellular proteins required 2+r excitation-contraction coupling to occur are:
1) L-type Ca channel (Ca 1V2). allows Ca entry into clefts adjacent to RYR2 channels
2) ryanodine receptor (RyR2)
3) Na /Ca 2+ exchanger (NCX1)
4) SR Ca ATPase (SERCA2a), phospholamban and sarcolipin
5) contractile protein machinery; myosin, actin, troponins, tropomyosin
(Steps 7-9 take place simultaneously.step 7 is rate-limiting).