ISOPROTERENOL POTENTIATES SYNAPTIC TRANSMISSION PRIMARILY BY ENHANCING PRESYNAPTIC CALCIUM INFLUX VIA P-TYPE AND OR Q-TYPE CALCIUM CHANNELSIN THE RAT AMYGDALA/

The effects of selective beta-adrenergic receptor agonist isoprotereno l (Iso) on neuronal excitability and synaptic transmission were invest igated in brain slices of rat amygdala. Iso (15 mu M) produced a long- lasting enhancement of the EPSP that was not blocked by pretreatment w ith 20 mu M D-2-amino-5-phosphonovalerate (D-APV) alone or D-APV in co mbination with kynuretic acid (1 mM). The sensitivity of postsynaptic neurons to the glutamate receptor agonist AMPA was unchanged by Iso pr etreatment. Superfusion of Iso reversibly blocked the after-hyperpolar ization (AHP) that followed a depolarizing current pulse and caused mo re action potential firing. Intracellular application of a selective i nhibitor of the catalytic subunit of cAMP-dependent protein kinase A b locked the effect of Iso on the AHP, whereas Iso-induced potentiation was entirely normal in the same neuron. In addition, Iso decreased the magnitude of paired-pulse facilitation, which is consistent with a pr esynaptic mode of action. Substituting the Mg2+ for Ca2+ in the medium completely abolished the Iso-induced enhancement of the EPSP. The eff ect of Iso also was blocked by low concentrations of omega-agatoxin-IV A, but not by nifedipine or omega-conotoxin-GVIA. These results sugges t that Iso enhances synaptic transmission in the amygdala via a presyn aptic site of action: the mechanism underlying the potentiating effect likely is attributable to an increased Ca2+ influx through P- and/or Q-type Ca2+ channels.