Expression and differential distribution of the shaker-related voltage-gated potassium channel family (KV1.x) in human hippocampus and neocortex
BMC Pharmacology volume 11, Article number: A27 (2011)
All excitable cells express voltage-gated potassium (KV) channels; in neurons they play an essential role in setting the resting membrane potential, controlling the firing frequency and duration of action potentials, and modulate neurotransmitter release. Due to this critical function as regulators of neuronal excitability, mutations and/or deletions in potassium channel subunit genes are associated with diverse clinical phenotypes (channelopathies), including seizure or movement disorders in both humans and animals. Additionally, voltage-gated potassium channels might play a crucial role in neurodegenerative and psychiatric disorders. For this reason, a better understanding of the occurrence and specific distribution of voltage-gated potassium channels would be highly necessary. Several members of the KV1 subfamily have been found, but only KV1.1, KV1.2, KV1.4 and KV1.6 are widely expressed in the CNS in both human and rodent brain. However, unlike to rodents, little is known regarding the regional localization of these four members of the KV1 subfamily in human brain. Therefore we investigated, for the first time, the distribution of these four KV1 channel subtypes in human neocortex and hippocampus, which are known for their vulnerability to epilepsy and their importance for learning, memory and cognitive processes.
Methods and results
To examine the relative expression levels of the KV1.1, KV1.2, KV1.4 and KV1.6 proteins in human as well in mouse brain and to determine the specificity of each individual α-subunit antibody for human brain tissue, Western blots were conducted. Individual expression patterns for each KV1 channel subtype were established by immunohistochemistry using polyclonal anti-KV1.1, KV1.2, KV1.4, and KV1.6 as primary antibodies. We found that the staining patterns of these four KV1 channel subunits overlap in some areas but each KV channel subunit shows a unique pattern of distribution in human cortex and hippocampus. The pyramidal cell bodies of cornu Ammonis (CA) 1–3 areas and the granule cell bodies of the dentate gyrus were strongly immunoreactive for KV1.1, KV1.2, KV1.4 and KV1.6. Varying degrees of immunoreactivity were also found in other layers, such the inner and outer molecular layer, stratum lacunosum and stratum oriens.
Precise knowledge of the differential distribution of KV1 channels in human brain may provide useful data for future investigations on common pathological conditions such as epilepsy and neurodegenerative disorders.
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Leitner, I., Wietzorrek, G., Trieb, M. et al. Expression and differential distribution of the shaker-related voltage-gated potassium channel family (KV1.x) in human hippocampus and neocortex. BMC Pharmacol 11 (Suppl 2), A27 (2011). https://doi.org/10.1186/1471-2210-11-S2-A27