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Structure and functional expression of a new member of the tetrodotoxin‐sensitive voltage‐activated sodium channel family from human neuroendocrine cells.
Author(s) -
Klugbauer N.,
Lacinova L.,
Flockerzi V.,
Hofmann F.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb07091.x
Subject(s) - biology , sodium channel , microbiology and biotechnology , tetrodotoxin , endocrinology , medicine , veratridine , g alpha subunit , sodium , protein subunit , biochemistry , gene , chemistry , organic chemistry
A member of a new subclass of the voltage‐activated sodium channel genes has been cloned from the human medullary thyroid carcinoma (hMTC) cell line. The cDNA of hNE‐Na (human neuroendocrine sodium channel) encodes a 1977 amino acid protein which phylogenetically represents a link between sodium channels isolated from skeletal muscle and brain. The hNE‐Na alpha subunit was transiently expressed in human embryonic kidney cells either alone or in combination with the human sodium channel beta 1 subunit. The channel exhibited rapid activation and inactivation kinetics, and was blocked by tetrodotoxin and cadmium with IC50 values of 24.5 nM and 1.1 mM, respectively. Action potentials were generated in cells expressing high levels of hNE‐Na. Northern blot and reverse transcription‐polymerase chain reaction (RT‐PCR) analyses demonstrated its expression in hMTC cells, in a C‐cell carcinoma, and in thyroid and adrenal gland. Transcripts were not identified in pituitary gland, brain, heart, liver or kidney, indicating that the hNE‐Na is a sodium channel solely expressed in neuroendocrine cells.