Modulation of Na+channel inactivation by the ?1 subunit: A deletion analysis

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Abstract
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.