Expression of Kv1 potassium channels in mouse hippocampal primary cultures: Development and activity-dependent regulation

Excitability and discharge behavior of neurons depends on the highly variab le expression pattern of voltage-dependent potassium (Kv) channels througho ut the nervous system. To learn more about distribution, development, and a ctivity-dependent regulation of Kv channel subunit expression in the rodent hippocampus, we studied the protein expression of members of the Kv1 subfa mily in mouse hippocampus in situ and in primary cultures. In adult hippocampus, Kv1 (1-6) channel alpha-subunits were present, wherea s at postnatal day 2, none of these proteins could be detected in CA1-CA3 a nd dentate gyrus. Kv1.1 was the first channel to be observed at postnatal d ay 6. The delayed postnatal expression and most of the subcellular distribu tion observed in hippocampal sections were mimicked by cultured hippocampal neurons in which Kv channels appeared only after 10 days in vitro. This de velopmental upregulation was paralleled by a dramatic increase in total Kcurrent, as well as an elevated GABA release in the presence of 4-aminopyri dine. Thus, the developmental profile, subcellular localization, and functi onality of Kv1 channels in primary culture of hippocampus closely resembles the in situ situation. Impairing secretion by clostridial neurotoxins or blocking activity by tetr odotoxin inhibited the expression of Kv1.1, Kv1.2, and Kv1.4, whereas the o ther Kv1 channels still appeared. This activity-dependent depression was on ly observed before the initial appearance of the respective channels and lo st after they had been expressed. Our data show that hippocampal neurons in culture are a convenient model to study the developmental expression and regulation of Kv1 channels. The ont ogenetic regulation and the activity-dependent expression of Kv1.1, Kv1.2, and Kv1.4 indicate that neuronal activity plays a crucial role for the deve lopment of the mature Kv channel pattern in hippocampal neurons.