Extended Data Figure 6. Shark K_V voltage sensor domain relaxation.

a. Q_OFF kinetics following either 10 ms or 1 ms 40 mV activating prepulses. Purple traces indicate deactivation at −50 mV. Arrow indicates when current properties were measured during voltage protocol.

b. Average Q_OFF kinetics were faster in shark (red) compared with human (black) during deactivation following 40mV prepulses of 25, 10, or 5 ms duration, but were of similar rates following 1ms activating prepulses. Kinetics were measured at voltages that decreased in 10mV increments from 40mV. n = 9, p < 0.0001 for contribution of orthologue identity to series variance at 25, 10, or 5 ms, but no significant difference was observed at 1 ms, two-way ANOVA with post hoc Bonferroni test.

c. Shark K_V1.3 Q_OFF kinetics were relatively unaffected by activating voltage pulse duration while human K_V1.3 entered a proposed ‘relaxed’ state resulting in slowing of Q_OFF with increasing pulse length. Deactivation was measured at −100 mV following a series of 40 mV voltage pulses of varying duration from 0.5 ms to 30 ms.

d. Average Q_OFF kinetics in response to indicated voltage pulse lengths. n = 6, p < 0.0001 for comparison of orthologue Q_OFF kinetics following a 30ms voltage pulse.

e. Hypothetical model of shark and human K_V1.3. Compared with its human orthologue, shark K_V1.3 exhibits reduced voltage sensor domain relaxation, which stabilizes pore opening in human K_V1.3. Reduced voltage sensor relaxation is indicated by dotted lines to suggest that this state(s) may occur to a lesser extent in the shark orthologue. Thus, compared with human K_V1.3, the shark orthologue requires relatively less repolarizing voltage to more quickly return to a resting/closed state.

All data represented as mean ± s.e.m.