Tj. Hawke et al., Paraxanthine, a caffeine metabolite, dose dependently increases [Ca2+](i) in skeletal muscle, J APP PHYSL, 89(6), 2000, pp. 2312-2317
It was hypothesized that the caffeine derivative paraxanthine results in su
bcontracture increases in intracellular calcium concentration ([Ca2+](i)) i
n resting skeletal muscle. Single fibers obtained from mouse flexor digitor
um brevis were loaded with a fluorescent Ca2+ indicator, indo l-acetoxymeth
yl ester. After a stable baseline was recorded, the fiber was superfused wi
th physiological salt solution (Tyrode) containing 0.5, 1.0, 2.5, or 5 mM p
araxanthine, resulting in [Ca2+](i) increases of 6.4 +/- 2.5, 9.7 +/- 3.6,
26.8 +/- 11.7, and 39.6 +/- 9.6 nM, respectively. The increases in [Ca2+](i
) were transient and were also observed with exposure to 5 mM theophylline
and theobromine. Six fibers were exposed to 5 mM paraxanthine followed by 5
mM paraxanthine in the presence of 10 mM procaine (sarcoplasmic reticulum
Ca2+ release channel blocker). There was no increase from baseline [Ca2+](i
) when fibers were superfused with paraxanthine and procaine, suggesting th
at the sarcoplasmic reticulum is the primary Ca2+ source in the paraxanthin
e-induced response. In separate experiments, intact flexor digitorum brevis
(n. = 13) loaded with indo l-acetoxymethyl ester had a significant increas
e in [Ca2+](i) with exposure to 0.01 mM paraxanthine. It is concluded that
physiological and low pharmacological concentrations of paraxanthine result
in transient, subcontracture increases in [Ca2+](i) in resting skeletal mu
scle, the magnitude of which is related to paraxanthine concentration.