THE HEART SODIUM-CHANNEL PHENOTYPE FOR INACTIVATION AND LIDOCAINE BLOCK

The heart Na channel, although resembling other voltage-gated Na chann els, has important functional and structural differences. For heart ch annels expressed in oocytes, the midpoint of the inactivation relation ship was 13 mV negative to that of rat skeletal muscle Na channels, an d sensitivity to tonic lidocaine block was approximately 5 times more sensitive for heart. Co-expression with the beta subunit increased the difference in inactivation midpoint to 24 mV, largely by changing the midpoint of the rat skeletal muscle channel by 10 mV in the positive direction. Co-expression with beta 1 decreased lidocaine sensitivity f or heart but not for skeletal muscle Na channels, and decreased but di d not eliminate the greater heart sensitivity to lidocaine block. The differences in inactivation are likely to account for some, but not al l, of the differences in lidocaine sensitivity. This cardiac phenotype is important for the role the channel plays in cardiac physiology and pathophysiology, and also may lead to elucidation of structure-functi on relationships