Abstract
The main aim was to investigate the effects of raised [K+]o on contraction of isolated non-fatigued skeletal muscle at 37°C and 25°C to assess the physiological significance of K+ in fatigue. Mouse soleus muscles equilibrated at 25°C had good mechanical stability when temperature was elevated to 37°C. The main findings at 37°C vis-à-vis 25°C were as follows. When [K+]o was raised from 4 to 7 mM, there was greater twitch potentiation, but no significant difference in peak tetanic force. At 10 mM [K+]o there was (1) a faster time course for the decline of peak tetanic force, (2) a greater steady-state depression of twitches and tetani, (3) an increase of peak force over 50–200 Hz (whereas it decreased at 25°C), (4) significant tetanus restoration when stimulus pulse duration increased from 0.1 to 0.25 ms and (5) greater depolarisation of layer-2 fibres, with no repolarisation of surface fibres. These combined data strengthen the proposal that a large run-down of the K+ gradient contributes to severe fatigue at physiological temperatures via depolarisation and impaired sarcolemmal excitability. Moreover, terbutaline, a β2-adrenergic agonist, induced a slightly greater and more rapid, but transient, restoration of peak tetanic force at 10 mM [K+]o at 37°C vis-à-vis 25°C. A right shift of the twitch force–stimulation strength relationship at 10 mM [K+]o was partially reversed with terbutaline to confer the protective effect. Thus, catecholamines are likely to stimulate the Na+–K+ pump more powerfully at 37°C to restore excitability and attenuate, but not prevent, the detrimental effects of K+.
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Acknowledgements
We gratefully thank Astra Pharmaceuticals for the donation of terbutaline, along with Dane Gerneke and Peter Mellow for graphical assistance. The work was supported by a grant from the Lotteries Grant Board of New Zealand.
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Appendix
Appendix
We quantified the expected effects of temperature on K+ diffusion into isolated whole soleus muscles based on the following assumptions and approximations.
- 1.
The diffusion constant of K+ in a 0.15 M solution at 25°C is D K+(s) = 1.846 × 10−5 cm2 s−1 (estimated by linear interpolation between the values at 0.1 M = 1.844 × 10−5 and 1.0 M = 1.892 × 10−5): Table F-45 [16].
- 2.
The diffusion constant of K+ in muscle is given by:
$${D_{{{\rm{K}} + ({\rm{m}})}} = {\phi \over {{\gamma}^{2} }}D_{{{\rm{K}} + ({\rm{s}})}} }$$where ϕ is the fraction of muscle occupied by extracellular space and γ = π/2 is the tortuosity factor for a muscle composed of parallel cylindrical fibres (i.e. the increase of length of the diffusion path imposed by the cellular nature of whole muscle) [32]. Thus
$$ {D_{{{\rm{K}} + \left( {\rm{m}} \right) }}} = {1}.{5}0{6} \times {1}{0^{{ - {6}}}}\,{\hbox{c}}{{\hbox{m}}^{{2}}}\,{{\hbox{s}}^{{ - {1}}}}\,{\hbox{at}}\,{25}^\circ {\hbox{C}}. $$ - 3.
The Q10 of K+ diffusivity is 1.2 (in the temperature range 14–25°C) [26].
- 4.
Hence, the K+ diffusion constant at 37°C is:
$$ {D_{{{\rm{K + }}}}} = 1.506\, \times \,{10^{{ - 6}}}\, \times 1.2^{\frac{{\left( {37 - 25} \right)}}{{10}} } {\hbox{c}}{{\hbox{m}}^{{2}}}\,{{\hbox{s}}^{{ - 1}}} = 1.867\,{\hbox{c}}{{\hbox{m}}^2}\,{{\hbox{s}}^{{ - 1}}} $$ - 5.
Mouse soleus muscle can be approximated by a cylinder of radius 0.5 mm.
From these latter two values and using Fig. 5.3 (P 74) of Crank [23], it is possible to estimate the time required for [K+]o to reach 90% of its final value at a depth of 60 μm from the surface (i.e. in layer-2 fibres) in response to a step change of concentration from 4 mM to 10 mM on the muscle surface. We calculate these time intervals to be about 4 min at 25°C and 3 min at 37°C. By contrast, the time required to reach 90% on the axis is calculated to be 10 min at 37°C and 13 min at 25°C.
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Cairns, S.P., Leader, J.P. & Loiselle, D.S. Exacerbated potassium-induced paralysis of mouse soleus muscle at 37°C vis-à-vis 25°C: implications for fatigue. Pflugers Arch - Eur J Physiol 461, 469–479 (2011). https://doi.org/10.1007/s00424-011-0927-4
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DOI: https://doi.org/10.1007/s00424-011-0927-4