Possible role of the transverse tubules in accumulating calcium released from the terminal cisternae by stimulation and drugs.

The size of the rapidly exchanging and slowly exchanging Ca2+ pools were estimated in frog sartorius muscles. A new technique using Sr2+ to extract the rapidly exchanging pool was used. The method avoids problems of kinetic analysis. The results showed that stimulation causes Ca2+ to be translocated from a compartment which exchanges with a time constant of 800 min to a compartment that can be washed out in 15 min. This is likely a transfer from the terminal cisternae to the transverse tubule. Calculations show that this would represent 0.9% of the Ca2+ released in each twitch. After 300 twitches produced by a 1-Hz stimulation, this accumulation could have increased the Ca concentration in the transverse tubules to 70 mM. A marked increase of Ca2+ concentration of this magnitude in the transverse tubules would raise the mechanical threshold for excitation--contraction coupling and would decrease the efficiency of coupling between contraction and excitation. This could be the explanation of the fatigue observed during this kind of stimulation.