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The hyperpolarization-activated cation current Ih is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown. We used cell-attached patch recordings to determine the localization profile of Ih along the somatodendritic axis of nigral dopamine neurons in slices from young rats. Ih density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma and axon-lacking dendrites. Dual current-clamp recordings revealed a similar contribution of Ih to the waveform of single excitatory postsynaptic potentials throughout the somatodendritic domain. The Ih blocker ZD 7288 increased the temporal summation in all dendrites with a comparable effect in axon- and non-axon dendrites. The strategic position of Ih in the proximity of the axon may influence importantly transitions between pacemaker and bursting activities and consequently the downstream release of dopamine.
Neuronal Kv7 channels (also termed KCNQ channels) are the molecular correlate of the M-current. The Kv7 channels activate at rather negative membrane potentials (< or = 60 mV), thereby 'fine-tuning' the resting membrane potential. The Kv7 channels are widely expressed in the brain with the Kv7.2, Kv7.3 and Kv7.5 channels being the most abundant. The Kv7.4 subunit has the most restricted brain regional expression being present in discrete nuclei of brainstem only. Kv7 channels are expressed at different subcellular locations, being on both somatodendritic, axonal and terminal sites. This complex subcellular distribution of Kv7 channels enables them to participate in both pre- and postsynaptic modulation of basal and stimulated excitatory neurotransmission. Activation of neuronal Kv7 channels limits repetitive firing thereby potentially limiting the generation of long bursts, with subsequent inhibition of monoaminergic neurotransmitter release. In this review, we focus on the influence of Kv7 channels on dopaminergic and serotonergic neurotransmission. The data suggest a novel action of Kv7 channel openers which could translate into having therapeutic value in the treatment of disease states characterized by overactivity of dopaminergic (e.g. schizophrenia and drug abuse) and serotonergic neurotransmission (e.g. anxiety).
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