Hippocampal ether-à-go-go1 potassium channels blockade: Effects in the startle reflex and prepulse inhibition

Abstract

Recently, our group described the ether-à-go-go1(Eag1) voltage-gated potassium (K(+)) channel (Kv10.1) expression in the dopaminergic cells indicating that these channels are part of the diversified group of ion channels related to dopaminergic neurons function. The increase of dopamine neurotransmission induces a reduction in the prepulse inhibition (PPI) of the acoustic startle reflex in rodents, which is a reliable index of sensorimotor gating deficits. The PPI response has been reported to be abnormally reduced in schizophrenia patients. The role of Eag1 K(+) channels in the PPI reaction had not been revealed until now, albeit the singular distribution of Eag1 in the dentate gyrus of the hippocampus and the hippocampal regulation of the startle reflex and PPI. The aim of this work was to investigate if Eag1 blockade on hippocampus modifies the PPI-disruptive effects of apomorphine in Wistar rats. Bilateral injection of anti-Eag1 single-chain antibody into the dentate gyrus of hippocampus did not modify apomorphine-disruptive effects in the PPI response. However, Eag1 antibody completely restored the startle amplitude decrease revealed after dentate gyrus surgery. These potentially biological important phenomenon merits further investigation regarding the role of Eag1 K(+) channels, mainly, on startle reflex modulation, since the physiological role of these channels remain obscure.

Eag1 K+ Channel: Endogenous Regulation and Functions in Nervous System

“…The deficiency of EAG1 only caused a mild hyperactivity and longer-lasting haloperidol-induced catalepsy but did not affect amphetamine sensitization and withdrawal and the reactivity to apomorphine and haloperidol in the prepulse inhibition (PPI) tests or to antidepressants in the haloperidol-induced catalepsy [96]. Consistently, Issy et al [97] also found that injection of anti-EAG1 antibody into the dentate gyrus of hippocampus did not modify apomorphine-disruptive effects in the PPI response. However, it is noteworthy that the EAG1 antibody completely restored the startle amplitude decrease revealed after dentate gyrus surgery.…”