Modulation of Na⁺channel inactivation by the β₁ subunit: A deletion analysis

Na⁺ currents recorded from Xenopus oocytes expressing the Na⁺ channel α subunit alone inactivate with two exponential components. The slow component predominates in monomeric channels, while coexpression with the β₁ subunit favors the fast component. Macropatch recordings show that the relative rates of these components are much greater than previously estimated from two-electrode measurements (≈30-fold vs ≈5-fold). A re-assessment of steady-state inactivation, h_∞(V), shows that there is no depolarized shift of the slow component, provided a sufficiently long prepulse duration and repetition interval are used to achieve steady-state entry and recovery from inactivation, respectively. Deletion mutagenesis of the β₁ subunit was used to define which regions of the subunit are required to modulate inactivation kinetics. The carboxy tail, comprising the entire predicted intracellular domain, can be deleted without a loss of activity; whereas small deletions in the extracellular amino domain or the signal peptide totally disrupt function.