Figure 1.

A schematic of purinergic autocrine regulation of CA3 pyramidal cell excitability. A: With abundant intracellular ATP and moderately reduced extracellular glucose - a scenario a ketogenic diet is thought to produce: (1) ATP is released directly via pannexin hemichannels, and (2) released ATP is dephosphorylated subsequently to adenosine (2) which activates adenosine A₁Rs (3). This in turn opens K_ATP channels which hyperpolarizes the membrane, and decreases excitability (4). In addition to these autocrine postsynaptic effects, the elevated adenosine can function in a paracrine manner to reduce neurotransmitter release from afferent axon terminals. Adapted and modified from Kawamura et al., 2010.