Cloning, distribution and functional analysis of the type III sodium channel from human brain

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 prot ein (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, cerebellum, hippo campus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage depend ence and kinetics of activation were found to be similar to that of type II . The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials a nd were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced current s with a prominent persistent component, which were similar to those report ed for rat type II [Ma at al. (1997) Neuron, 19, 443-452]. However, unlike type II, this was prominent even in the absence of coexpressed G-proteins, suggesting type III may adopt this gating mode more readily. The distinct p roperties of the channel, together with its wide distribution in adult brai n, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions.