The response of NaV1.3 sodium channels to ramp stimuli: multiple components and mechanisms

NaV1.3 voltage-gated sodium channels have been shown to be expressed at increased levels within axotomized dorsal root ganglion neurons and within injured axons within neuromas and have been implicated in neuropathic pain. Like a number of other sodium channel isoforms, NaV1.3 channels produce a robust response to slow ramplike stimuli. Here we show that the response of NaV1.3 to ramp stimuli consists of two components: an early component, dependent upon ramp rate, that corresponds to a window current that is dependent upon closed-state inactivation; and a second component at more depolarized potentials that is correlated with persistent current which is detected for many tens of milliseconds after the start of a depolarizing pulse. We also assessed the K354Q NaV1.3 epilepsy-associated mutant channel, which is known to display an enhanced persistent current and demonstrate a strong correlation with the second component of the ramp response. Our results show that a single sodium channel isoform can produce a ramp response with multiple components, reflecting multiple mechanisms, and suggest that the upregulated expression of NaV1.3 in axotomized dorsal root ganglion neurons and enhanced ramp current in K354Q mutant channels can contribute in several ways to hyperexcitability and abnormal spontaneous firing that contribute to hyperexcitability disorders, such as epilepsy and neuropathic pain.

3D IMAGE RECONSTRUCTION FOR SUBMERGED OBJECTS USING RAMP RESPONSE SIGNATURES

Underwater acoustical imaging techniques and the inverse analysis of acoustic scattering problems have now found many important engineering applications. Based on the physical optics approximation, the ramp response signal can be proven that it is proportional to the profile function of the scatterer, which is defined as the area of cross section of the object perpendicular to the direction of wave propagation. The image synthesis technique named as the approximate limiting surface technique is applied to generated underwater objects by using the ramp responses of the objects. The modification should be made by an iterative procedure which will adjust the parameters of each surface and will yield a result until the profile functions of this generated image at all looking angles are consistent with the input ones. Several typical objects are presented to demonstrate the process of the 3D image generation and the results indicate that the qualities of the final images are quite acceptable. The further research work is to build an automatic iterative mechanism to generate the final image for a submerged object.