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Molecular correlates of the M-current in cultured rat hippocampal neurons

M. M. Shah, M. Mistry, S. J. Marsh, D. A. Brown and P. Delmas

M-type K⁺ currents (I_K(M)) play a key role in regulating neuronal excitability. In sympathetic neurons, M-channels are thought to be composed of a heteromeric assembly of KCNQ2 and KCNQ3 K⁺ channel subunits. Here, we have tried to identify the KCNQ subunits that are involved in the generation of I_K(M) in hippocampal pyramidal neurons cultured from 5- to 7-day-old rats. RT-PCR of either CA1 or CA3 regions revealed the presence of KCNQ2, KCNQ3, KCNQ4 and KCNQ5 subunits. Single-cell PCR of dissociated hippocampal pyramidal neurons gave detectable signals for only KCNQ2, KCNQ3 and KCNQ5; where tested, most also expressed mRNA for the vesicular glutamate transporter VGLUT1. Staining for KCNQ2 and KCNQ5 protein showed punctate fluorescence on both the somata and dendrites of hippocampal neurons. Staining for KCNQ3 was diffusely distributed whereas KCNQ4 was undetectable. In perforated patch recordings, linopirdine, a specific M-channel blocker, fully inhibited I_K(M) with an IC₅₀ of 3.6 ± 1.5 µM. In 70 % of these cells, TEA fully suppressed I_K(M) with an IC₅₀ of 0.7 ± 0.1 mM. In the remaining cells, TEA maximally reduced I_K(M) by only 59.7 ± 5.2 % with an IC₅₀ of 1.4 ± 0.3 mM; residual I_K(M) was abolished by linopirdine. Our data suggest that KCNQ2, KCNQ3 and KCNQ5 subunits contribute to I_K(M) in these neurons and that the variations in TEA sensitivity may reflect differential expression of KCNQ2, KCNQ3 and KCNQ5 subunits.

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