Adenosine and its derivatives may induce acute changes, i.e., injury and de
ath, in muscle cells. In the present work, we evaluated the intracellular c
alcium concentration in C2C12 myogenic cells differentiated in vitro to for
m myotubes and exposed to a metabolically stable analogue of adenosine, g-c
hloro-adenosine. The compound was able to significantly modify ionic homeos
tasis by sensitizing muscle cells to the excitatory amino acid glutamate. A
single exposure to glutamate led to a marked increase in intracellular cal
cium level. This is the first demonstration that adenosine analogues can re
gulate muscle cell integrity and function via an indirect increase of intra
cellular calcium ions. (C) 2000 academic Press.