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Antisera directed against unique peptide regions from each of the human brain voltage-gated sodium channel alpha subunits were generated. In immunoblots these were found to be highly specific for the corresponding recombinant polypeptides and to recognise the native holoprotein in human brain membrane preparations. These antisera were used to perform a(More)
The distribution of mRNAs encoding voltage-gated sodium channel alpha subunits (I, II, III, and VI) and beta subunits (beta1 and beta2) was studied in selected regions of the human brain by Northern blot and in situ hybridisation experiments. Northern blot analysis showed that all regions studied exhibited heterogenous expression of sodium channel(More)
We have cloned and expressed the full-length human Na(V)1.6 sodium channel cDNA. Northern analysis showed that the hNa(V)1.6 gene, like its rodent orthologues, is abundantly expressed in adult brain but not other tissues including heart and skeletal muscle. Within the adult brain, hNa(V)1.6 mRNA is widely expressed with particularly high levels in the(More)
Studies with animal seizure models have indicated that changes in temporal and spatial expression of voltage-gated sodium channels may be important in the pathology of epilepsy. Here, by using in situ hybridisation with previously characterised subtype-selective oligonucleotide probes [Whitaker et al. (2000) J. Comp. Neurol. 422, 123-139], we have compared(More)
The human brain voltage-gated Na+ channel type IIA alpha subunit was cloned and stably expressed in Chinese hamster ovary cells and its biophysical and pharmacological properties were studied using whole-cell voltage-clamp. Fast, transient inward currents of up to -8,000 pA were elicited by membrane depolarization of the recombinant cells. Channels(More)
Sea anemones are an important source of various biologically active peptides, and it is known that ATX-II from Anemonia sulcata slows sodium current inactivation. Using six different sodium channel genes (from Nav1.1 to Nav1.6), we investigated the differential selectivity of the toxins AFT-II (purified from Anthopleura fuscoviridis) and Bc-III (purified(More)
The type III voltage-gated sodium channel was cloned from human brain. The full-length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus,(More)
PURPOSE The transient and the persistent Na(+) current play a distinct role in neuronal excitability. Several antiepileptic drugs (AEDs) modulate the transient Na(+) current and block the persistent Na(+) current; both effects contribute to their antiepileptic properties. The interactions of the AEDs carbamazepine (CBZ) and topiramate (TPM) with the(More)
Voltage-gated sodium channels are responsible for the upstroke of the action potential in most excitable cells, and their fast inactivation is essential for controlling electrical signaling. In addition, a noninactivating, persistent component of sodium current, I(NaP), has been implicated in integrative functions of neurons including threshold for firing,(More)