Hypercapnia and Hypocapnia Modulate Hippocampal Epileptiform Activity in Area CA3 via Adenosine A1 and ATP Receptors
Extracellular recordings of synchronized bursting in area CA3. (A) Hypercapnia (20% CO2) reversibly attenuates bursting. Inset, left: (A1) Example of a single burst recorded during control conditions (5% CO2) (scale bars, 1 mV, 50 ms for all). (A2) Example of extracellular recording during hypercapnia, no bursts present. (Note: exact location of samples indicated on trace below.) Inset, right: Burst frequency during control and hypercapnic conditions. (B) Blocking adenosine A1 receptors with DPCPX increases tonic firing, and hypercapnia (20% CO2) did not attenuate bursting during adenosine A1 receptor blockade. Inset, left: (B1) Example of a single burst recorded during control conditions (5% CO2) with application of DPCPX. (B2) Example of a single burst recorded during hypercapnia with application of DPCPX, bursts still present. Inset, right: Burst frequency during control/DPCPX and hypercapnic/DPCPX conditions. (C) Hypocapnia (2% CO2) increases bursting frequency. Inset, left: (C1) Example of a single burst recorded during control conditions (5% CO2). (C2) Example of extracellular recording during hypocapnia. Inset, right: Burst frequency during control and hypocapnic conditions. (D) Blocking adenosine A1 receptors and ATP receptors attenuates hypocapnia-induced increases in bursting frequency. Inset, left: (D1) Example of a single burst recorded during control conditions (5% CO2). (D2) Example of extracellular recording during hypocapnia. Inset, right: Burst frequency does not change during hypocapnia when adenosine A1 receptors and ATP receptors are blocked. (E) Average percent change in burst frequency. Hypercapnia (20% CO2; n = 6) attenuates bursting, but burst frequency is not altered by hypercapnia when adenosine A1 receptors are blocked with DPCPX (n = 4; **p < 0.01, ANOVA, Fisher PLSD). Hypocapnia (2% CO2) increases average burst frequency from control levels (n = 7). This increase in burst frequency is prevented when DPCPX and suramin are applied prior to exposure to 2% CO2 (n = 10; ***p < 0.001, ANOVA, Fisher PLSD). (F) Attenuation of bursting by hypercapnic buffer was not due to decreased oxygen (n = 5; ***p < 0.001, Student's t test). Error bars indicate standard error.