Tissue distribution and functional expression of the human voltage-gated sodium channel beta3 subunit

This study investigated the distribution of beta3 in human tissues and the functional effects of the human beta3 subunit on the gating properties of brain and skeletal muscle alpha subunits. Using RT-PCR of human cDNA panels, beta3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both alphaIIA and SkM1 expressed in Xenopus oocytes inactivated with a time course described by two exponential components representing fast and slow gating modes, while co-expression of human beta3 with alphaIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of beta3 a greater proportion of alphaIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. beta3 caused a hyperpolarizing shift in the voltage dependence of inactivation of alphaIIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with beta3 was described by a single Boltzmann equation similar to one of the Boltzmann components for SkM1 expressed alone, with a small positive shift in V1/2 value and reduced slope factor. This is the first study demonstrating that beta3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle alpha subunit, SkM1.