Barium, Glibenclamide and CGS21680 Prevent Adenosine A₁ Receptor Changes of ES Coupling and Spike Threshold

Abstract

Activation of adenosine A₁ receptors raised spike thresholds and induced a dissociation of excitatory postsynaptic potential (EPSP) spike coupling in hippocampal pyramidal neurones. This effect could be prevented by activation of A_2A adenosine receptors. The A₁ receptor agonist N⁶-cyclopentyladenosine caused a dissociation of the EPSP spike coupling recorded extracellularly and increased the threshold for spike generation measured intracellularly. These effects were prevented by the A_2A receptor agonist CGS21680. A series of agents interfering with adenylate cyclase activity, protein kinase A or C, or nitric oxide synthase had no effect on these responses to N⁶-cyclopentyladenosine. Superfusion with barium or glibenclamide prevented both the dissociation of EPSP spike coupling and the increase of spike threshold. It is concluded that a barium- and glibenclamide-sensitive potassium current may be involved in the postsynaptic effects of A₁ receptors on spike threshold, and it is suggested that a similar suppression of a potassium current by A_2A receptors could underlie the inhibition of A₁ receptor responses.

Glutamate‐induced depression of EPSP–spike coupling in rat hippocampal CA1 neurons and modulation by adenosine receptors

“…One such possibility to account for the delayed modulatory effects on recovery is that a change occurs in the number, distribution or sensitivity of adenosine receptors in response to high concentrations of glutamate, especially involving receptors at synaptic regions where, as noted above, the results would be consistent with a change of E–S coupling (O’Kane & Stone, 1998, 2004). In particular, the results imply that there may be an increased sensitivity of postsynaptic adenosine receptors associated with E–S coupling, but not presynaptic adenosine receptors regulating transmitter release and EPSP generation.…”