Download effects of inhibitors of cell membrane calcium channels

EFFECTS OF INHIBITORS OF CELL MEMBRANE CALCIUM CHANNELS ON
HIGH-FREQUENCY FATIGUE OF FAST AND SLOW SKELETAL MUSCLES
Elena GERMINARIO1, Alessandra ESPOSITO1, Menotti MIDRIO1, Philip T. PALADE2,
Romeo BETTO3 and Daniela DANIELI1
1
Department of Human Anatomy and Physiology, University of Padova, Italy; 2
Departments of Physiology and Biophysics and of Pharmacology and Toxicology,
University of Texas Medical Branch, Galveston Texas; 3 C.N.R. Neuroscience Institute,
Muscle Biology and Physiopathology Unit, Padova, Italy.
This work investigated the role of extracellular Ca2+ influx through cell membrane Ca2+
channels during high-frequency fatigue (HFF) in slow and fast skeletal muscles of mice.
The study was performed in both innervated and in 14-day denervated soleus and EDL
muscles of CD1 mice (3-month old). Stimulation in nominally Ca2+-free conditions caused
a dramatic increase of fatigue in the slow-twitch soleus muscle, while in the presence of
high Ca2+ levels (5 mM) fatigue was reduced. In the fast-twitch EDL muscle, HFF was not
affected by external calcium levels either way. These results indicate that HFF of soleus
muscle is sensitive to the entry of Ca2+. The possible involvement of store-operated Ca2+
channels (SOCs), mechano-sensitive or stretch-activated cation channels (SACs), L-type
voltage-gated Ca2+ channels, and of P2X receptors in HFF development of soleus muscle
was investigated by using specific inhibitors. Calciseptine, a specific antagonist of the 1C
isoform of the DHPR, did not influence the development of HFF. Gadolinium, a blocker of
both SACs and SOCs, and a mixture of P2X receptor inhibitors significantly reduced
fatigability of soleus muscle. Thus, the protective action of extracellular Ca2+ in soleus
HFF appears to involve the activation of different channels. Interestingly, EDL muscle,
which is insensitive to extracellular Ca2+ became sensitive after 14 days of denervation
The work was supported by NIH (PP and DDB) and MIUR.