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1549361 
Journal Article 
Temperature-dependent release of ATP from human erythrocytes: mechanism for the control of local tissue perfusion 
Kalsi, KK; Gonzalez-Alonso, J 
2012 
Yes 
Experimental Physiology
ISSN: 0958-0670
EISSN: 1469-445X 
97 
3 
419-432 
22227202 
WOS:000300873500017 
Human limb muscle and skin blood flow increases
significantly with elevations in temperature, possibly through physiological processes that
involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the
release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in
temperature both in vitro and in vivo, and examined potential channel/transporters involved. To
investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were
heated in vitro to 33, 36, 39 and 42 degrees C. In vitro heating augmented plasma or bathing
solution ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples.
Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by
inhibitors of nucleoside transport or anion exchange. Heating blood to 42 degrees C enhanced (P <
0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in
RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during
exercise, increases in muscle temperature from 35 to 40 degrees C correlated strongly with
elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP
(r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in
arterial and venous samples heated to 39 degrees C. Our findings demonstrate that erythrocyte ATP
release is sensitive to physiological increases in temperature, possibly via activation of CFTR-
like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be
an important mechanism regulating human limb muscle and skin perfusion in conditions that alter
blood and tissue temperature.