Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

This study investigated the distribution of β3 in human tissues and the functional effects of the human β3 subunit on the gating properties of brain and skeletal muscle α subunits. Using RT-PCR of human cDNA panels, β3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both αIIA 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 β3 with αIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of β3 a greater proportion of αIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. β3 caused a hyperpolarizing shift in the voltage dependence of inactivation of αIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with β3 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 β3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle α subunit, SkM1.