Figure 3.

VGC operation is inherently mechanosensitive (MS). (A) Nav1.5 channel current accelerates reversibly with stretch; activation and inactivation rates both speed to the same extent (Gmax has been reached at −30 mV in this patch, so peak I_Na is unaffected by stretch, but activation and fast inactivation both reversibly accelerate; modified from Morris and Juranka, 2007a). (B) a Nav1.5 activation Boltzmann left-shifts reversibly with stretch. (C) Shaker (Kv1) and Shaker-ILT have different rate-limiting voltage transitions in the activation pathway. Stretch affects both, but it accelerates the (largely independent) movement of the Shaker voltage sensors, whereas it decelerates (the late concerted) movement of the voltage sensor in Shaker-ILT, as seen here for voltages near the foot and head of the respective G(V)s; in keeping with the acceleration vs deceleration, stretch left-shifts the Shaker Boltzmann and right-shifts the Shaker-ILT Boltzmann (not shown; see Reference Laitko et al., 2006). (D) In Shaker 5aa, voltage-dependent gating is two orders of magnitude slower than in Shaker (compare to C; note the different time scales), but since an independent (though sluggish) voltage-dependent transition is rate-limiting for activation, this mutant channel behaves like its “WT” counterpart (see Laitko and Morris, 2004). (E) HCN2 channels open with hyperpolarization, they close with depolarization, they have multiple open states and they exhibit pronounced hysteresis. Here HCN2 currents are studied by (i) ramp clamp, (ii) passive action potential clamp and (iii) classic step clamp (see Lin et al., 2007) for details. Upon a step depolarization (iii) from −140 to −40 mV, stretch accelerates channel closure. Gating currents show this transition to be analogous to the rate-limiting depolarization-induced “outward” voltage sensor motion in Kv Shaker.