Klugbauer et al. (1995) cloned a novel voltage-gated sodium channel, termed NENA, from a human medullary thyroid
carcinoma cell cDNA library. Sequence analysis revealed that the cDNA encodes a 1,977-amino acid polypeptide composed
of 4 domains, each with 6 transmembrane domains and 2 highly conserved pore-forming segments.
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Luteolysis
Comment
Bulling A et al 20000 identified an ovarian voltage-activated Na+-channel type and hints of its
involvement in luteolysis.
An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary
and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in
GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was
found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for
24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting
membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was
indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures
for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly
differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes
but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the
nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also
contain eNaCh mRNA. As observed in GC in culture, abundant secondary
lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh
activity and this form of cellular regression in vivo. Activation of
eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to
decreased CL function, a process that involves lysosomal activation and autophagy. These results
imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ
CL in the primate ovary during the menstrual cycle.