Experimental physiology

In isolated skeletal muscle, excitation may increase extracellular K+ 10-fold; how can contractility be maintained?

PMID 21123362


During excitation, isolated rat muscles undergo a net loss of cellular K(+), which cannot be cleared via capillaries and can only be cleared to a small extent via diffusion into the surrounding buffer. Therefore, K(+) accumulates in the extracellular space and can be quantified using flame photometry and compared with contractile performance in extensor digitorum longus (EDL) and soleus muscles. During electrical stimulation, extracellular potassium concentration ([K(+)](o)) shows a rapid early rise, followed by a slower increase, reflecting progressive loss of excitability. Thus, after 30 s of 60 Hz stimulation in EDL, where [K(+)](o) reaches 50 mm, increasing the pulse duration from 0.2 to 1.0 ms augments force by 172%. Excitation-induced cellular loss of K(+) coincides with an equivalent gain of Na(+), in keeping with the one-for-one exchange of Na(+) and K(+). This Na(+)-K(+) exchange is completely reversible and is not accompanied by changes in the (14)C-sucrose space or release of intracellular enzyme activity, indicating that it is not due to unspecific cellular leakage. In EDL, 60 s of 20 Hz stimulation induced force elevation and increased [K(+)](o) to 43-47 mm. The force elevation was suppressed by ouabain (10(-5)m), indicating that the Na(+)-K(+) pump contributes to maintenance of excitability. After 15 s of 60 Hz stimulation, resting net re-extrusion of Na(+) was 7.3-fold faster than basal Na(+) efflux. Bumetanide, which blocks Na(+)-K(+)-2Cl(-) cotransport, caused no change in force and K(+) contents, excitation-induced loss of K(+) or postexcitatory reaccumulation of K(+). Omission of Cl(-) increased the rate of force decline 14-fold. In conclusion, during repeated excitation, isolated rat muscles undergo a much greater increase in [K(+)](o) than previously reported, sufficient to explain loss of force. This K(+) is not cleared via Na(+)-K(+)-2Cl(-) cotransport, but rather via Na(+)-K(+) pumps and by processes depending on Cl(-) exchange. These mechanisms are essential for the maintenance of force during intense contractions in vivo, where the clearance of K(+) via the capillaries may be suppressed.

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