Craniofacial Muscles

3 Extraocular Muscle Structure and Function
43
contain SERCA1. Overall, calcium handling is also signi fi cantly different in EOM
than in limb and body skeletal muscles. The EOM are more resistant to necrosis
induced by elevated cytosolic calcium levels (Khurana et al. 1995 ; Zeiger et al.
2010 ) . This increased calcium buffering capacity in EOM is due to a combination
of factors: abundant sarcoplasmic reticulum (which increases SERCA content),
high concentrations of parvalbumin, a small cytosolic Ca 2+ -binding protein, and
mitochondria serving as fast Ca 2+ sinks (Andrade et al. 2005 ; Celio and Heizmann
1982 ) . This enhanced ability to regulate cytosolic Ca 2+ concentration plays a role in
controlling contractile amplitude in the EOM.
The EOM are constantly active, have some of the fastest contractile properties
(Close and Luff 1974 ) , are very fatigue-resistant (Fuchs and Binder 1983 ) , and
while they normally need to produce only enough force to move the eye, they are
not intrinsically weaker than limb skeletal muscles (Frueh et al. 2001 ) . The bases
for these properties as well as the maintenance of these properties during eye movements
are an area of continued investigation. It has long been known that the EOM
have an extremely high density of mitochondria compared to non-cranial skeletal
muscles (Mayr 1971 ; Davidowitz et al. 1980 ) . In addition, the EOM mitochondria
have a different mitochondrial biogenesis program than the one used by limb skeletal
muscle (Andrade et al. 2005 ) . Despite their large mitochondrial volume density,
paradoxically the EOM mitochondria have lower respiratory capacity (Patel et al.
2009 ) . In addition, key enzymes controlling glycogen synthesis and breakdown are
repressed in the EOM, and glycogen content is correspondingly reduced (Porter
et al. 2001 ; Fischer et al. 2002 ) , suggesting that the EOM are probably less dependent
on glycogen as a metabolic fuel than other skeletal muscles. It is also possible
that the EOM rely on constant transport of blood-borne glucose and fatty acids
through their extensive microvascular network (Kjellgren et al. 2004 ). Overall, the
pattern is consistent with the EOM relying to a large extent on mitochondria as the
main source of energy under all conditions. One example is the use of lactate as a
substrate for its aerobic metabolism (Andrade and McMullen 2006 ) . In limb skeletal
muscles lactate is usually the end product of glycolysis and is associated with
muscle fatigue. In the EOM, the presence of lactate dehydrogenase B allows the
oxidation of lactate back to pyruvate for entry to the Krebs cycle; therefore, lactate
can sustain EOM activity and slow the progression of fatigue (Fig. 3.10 ).
The EOM contain high levels of both oxidative and glycolytic enzymes. An analysis
of serially sectioned and histochemically stained EOM myo fi bers demonstrated
that, except for the myo fi bers expressing MyHC-slow tonic, all fi bers express both
succinic dehydrogenase and a -glycerophosphate dehydrogenase (Asmussen et al.
2008 ) . This demonstrates that single EOM myo fi bers combine high levels of both
oxidative and glycolytic pathways, in stark contrast to limb skeletal muscle. When
each enzyme was plotted against myo fi ber area or whether the fi ber was fast or
slow, a continuum of fi bers emerged, with only the slow tonic-positive myo fi bers in
a group by themselves. Again it appears that the fi ber type system used in limb and
body skeletal muscles does not fi t the picture in EOM.