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LETTER TO THE EDITOR
According to this hypothesis, the elevated plasma glucose concentration is sensed by hSGLT3, which initiates membrane depolarization by increasing the inward diffusion of Na+ into the cell. Although the possibility exists that hSGLT3 may play a role in regulating membrane excitability during contractile activity, it is difficult to understand how an enhanced depolarization would be supportive in the context of our experimental conditions. In our protocol, participants engaged in prolonged submaximal cycling with and without glucose ingestion. Without glucose, our M-wave measurements indicate a compromised ability to maintain repetitive action potentials. There is much evidence to indicate that the loss of membrane excitability occurs as a result of an inability to transport Na+ out of and K+ into the cell following each action potential (2). The inability to reestablish transmembrane gradients for Na+ and K+ has been, in large part, attributed to a failure at the level of the Na+-K+-ATPase, the cation pump involved in the active transport of these cations (2). Conceivably, increases in the catalytic activity of the pump could be involved in protecting membrane excitation during the glucose condition. This is what we have found (6). With glucose supplementation, the maximal Na+-K+-ATPase activity (Vmax), assessed in vitro in homogenates using the 3-O-methylfluorescein phosphatase assay, was elevated. Increases in Vmax could allow a greater absolute catalytic activity of the pump at given Na+ and K+ concentrations. Unfortunately, limitations in the assay prevented us from determining whether alterations in the sensitivity of the enzyme to K+ and/or Na+ also occurred.
On the basis of the assumption that increases in Vmax of the enzyme are central to protecting membrane excitability, the question arises as to the mechanisms involved in elevating Vmax. Several possibilities exist. The elevated plasma glucose could act directly on the enzyme, either directly or via second messenger effects. However, evidence exists that, at least in the rat soleus muscle, high glucose levels result in a reduction in Vmax (1). Alternatively, the increase in Vmax could have been hormone-mediated, since the glucose condition resulted in higher serum insulin and lower plasma catecholamine (both norepinephrine and epinephrine) concentrations (6). These possibilities also seem remote. It has been shown that although insulin increases the translocation of active Na+-K+-ATPase subunits to the plasma membrane, increasing Vmax in plasma membrane fractions, it does not increase Vmax in homogenates (1). It is possible that the increase in Vmax in the plasma membrane fraction could account for the apparent beneficial effect of glucose on membrane excitability that we have observed. Catecholamines are known to increase Vmax via stimulation of β-receptors, ultimately resulting in increased phosphorylation of the 
-subunits (2). However, with glucose, the exercise-induced increases in the catecholamines were blunted.
Changes in Vmax might also occur via energy-mediated mechanisms. Given the importance of glucose as a substrate in working muscle, increased availability could attenuate any disruption in energy homeostasis and increases in metabolic by-product accumulation that could occur later in exercise as glycogen-reserves are depleted. This could be particularly important for the Na+-K+-ATPase given the fact that glycolysis is the predominant source of energy (7). This possibility is also remote since we found little differences between conditions in metabolic behavior, at least with the global measurements employed (4). Moreover, a disruption in energy homeostasis would be expected to be inhibitory to the enzyme not stimulatory. At present, the authors are not aware of any studies that have shown that the glucose sensor hSGLT3 can affect the catalytic activity of the pump and particularly the Vmax when measured in vitro.
FOOTNOTES
Address for reprint requests and other correspondence: H. Green, Dept. of Kinesiology, Univ. of Waterloo, Waterloo, Ontario, Canada N2L 3G1 (e-mail: green{at}healthy.uwaterloo.ca)
REFERENCES
-subunits in rat skeletal muscle. Endocrinology 142: 3474–3482, 2001.
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