Glucose reverses 2,4-dinitrophenol induced changes in action potentials and membrane currents of guinea pig ventricular cells via enhanced glycolysis.
The precise mechanism involved in the restoration by glucose of action potentials and membrane currents has not been established, so we studied it in single guinea pig ventricular cells under conditions of metabolic inhibition by 2,4-dinitrophenol (DNP). Application of DNP (50 mumol.litre-1) significantly shortened the action potential duration (APD) from 276.3 (SD 47.5) to 43.0(3.9) ms (n = 10). The increase in glucose concentration from 5.5 (control) to 22 mmol.litre-1 significantly restored the APD within 10 min, to 233.2(51.2) ms. In tight seal whole cell clamp studies, we found that DNP increased the steady state outward currents at potentials positive to -60 mV, and that this current was all but suppressed by 22 mmol.litre-1 glucose. The glucose induced recovery in the APD and membrane current was not seen in the presence of 2-deoxyglucose (2 mmol.litre-1), an inhibitor of glycolysis. Insulin (40 mIU.ml-1) reversed the DNP induced shortening of APD and abolished the increase in the outward current in the presence of 11 mmol.litre-1 glucose, though the application of glucose alone at this concentration failed to reverse these changes. Glucose (5.5 to 44 mmol.litre-1) did not directly affect single channel currents of ATP regulated K channels of the excised patch membrane in an outside out mode. These results suggest that the antagonising effects of glucose on the DNP induced alterations in APD and membrane currents are mediated by an increase in intracellular ATP concentration via enhanced glycolysis. Insulin might enhance this effect by facilitating the transport of glucose across the cell membrane.
Nakamura
S
S
Department of Physiology, Medical College of Oita, Japan.
Kiyosue
T
T
Arita
M
M
D019297:2,4-Dinitrophenol; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004140:Dinitrophenols / Q000037:antagonists & inhibitors*; D005947:Glucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D013997:Time Factors; D014475:Uncoupling Agents / Q000037:antagonists & inhibitors*
D004140:Dinitrophenols; D007328:Insulin; D007473:Ion Channels; D015221:Potassium Channels; D014475:Uncoupling Agents; D003847:Deoxyglucose; D005947:Glucose; D019297:2,4-Dinitrophenol