Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons

Pharmacological studies of glutamate receptor stimulation of the phosphoinositide (PI) system have demonstrated that this response is blocked by several agents: 2-amino-3-phosphonopropionate (AP3), phorbol esters and in some preparations pertussis toxin. In electrophysiological studies of CA1 pyramidal neurons, we have found that pertussis toxin and AP3 (1-2 mM) do not block either the membrane depolarization or inhibition of the slow afterhyperpolarization elicited by trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD; 30 μM), a selective agonist of the PI-linked glutamate receptor. However, phorbol 12,13-diacetate (1-1.5 μM) which itself blocks the slow afterhyperpolarization, completely blocks the membrane depolarizing response elicited by ACPD. These results add to growing evidence for heterogeneity among PI-linked glutamate receptor responses.