Fig. 4.

Involvement of glucose transporters and a glucose sensor in d-glucose sensing by neurons that are excitated by d-glucose (GE neurons). a A metabolism-dependent mechanism detected in rodents is shown. Increased d-glucose uptake at high extracellular glucose by a Glut transporter leads to an increase of intracellular glucose promoting ATP synthesis. Elevated intracellular ATP blocks an ATP-dependent K⁺ channel resulting in a decrease of the membrane potential. This promotes opening of the voltage-dependent Ca²⁺ channel VDCC. Increased intracellular Ca²⁺ induces the release of neurotransmitters. b A metabolism-independent mechanism observed in rodents is shown. Na⁺-d-glucose cotransport by Sglt1, Sglt2, or Sglt3b or binding of d-glucose to the glucose activated Na⁺/H⁺ ion channel Sglt3a leads to a depolarization of the plasma membrane and to an increase of Ca²⁺ uptake via VDCC. The increased intracellular Ca²⁺ concentration triggers the release of neurotransmitters. Ψ membrane potential