Figure 4.

Membrane trauma can irreversibly left-shift Nav channel operation, producing “leaky” Nav channels, probably because the resident bilayer gets more bleb-like, i.e., thinner, more disordered. (A) This phenomenon was first discovered from accidental damage to membranes while making gigaohm seals on oocytes. Here, Nav1.4 (without the auxiliary beta subunit) kinetics recorded in 4 patches from the same oocyte look radically different depending on the extent to which the membrane was mechanically traumatized during seal formation. Modifed from (Tabarean et al., 1999). (B) Cartoon suggesting that bleb formation leaves channels (dark ovals) in a bilayer environment that is on average thinner and (not specifically depicted but indicated by the lighter color) more disordered/fluid/symmetric-across-leaflets. In oocytes, Nav1.5 channels behave as if they are trafficked to disordered membrane (Morris and Juranka, 2007a; Wang et al., 2009; Banderali et al., 2010) and so do not show irreversible kinetic changes with stretch, but in HEK cells, stretch is largely traumatic for Nav1.5 channels (Beyder et al., 2010). (C) The trauma phenomenon also occurs for Nav1.6 in oocyte membranes and is summarized by coupled left-shift of the activation and steady-state inactivation curves as shown here (see Wang et al., 2009).