, Volume 441, Issue 4, pp 481-488

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

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Abstract.

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 V 1/2 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.

Received after revision: 16 August 2000
Electronic Publication