1. Sodium channel ionic current (I-Na) and gating current (I-g) were compar
ed for rat skeletal (rSkM1) and human heart Na+ channels (hH1a) heterologou
sly expressed in cultured mammalian cells at similar to 13 degrees C before
and after modification by site-3 toxins (Anthopleurin A and Anthopleurin B
).
2. For hH1a Na+ channels there was a concordance between the half-points (V
-1/2) of the peak conductance-voltage (G-V) relationship and the gating cha
rge-voltage (Q-V) relationship with no significant difference in half-point
s. In contrast, the half-point of the Q-V relationship for rSkM1. Na+ chann
els was shifted to more negative potentials compared with its G-V relations
hip with a significant difference in the half-points of -8 mV.
3. Site-3 toxins slowed the decay of I-Na in response to step depolarizatio
ns for both rSkM1 and hH1a Na+ channels. The half-point of the G-V relation
ship in rSkM1 Na+ channels was shifted by -8.0 mV while toxin modification
of hH1a Na+ channels produced a smaller ;hyperpolarizing shift of the V-1/2
by -3.7 mV.
4. Site-3 toxins reduced maximal gating charge (Q(max)) by 33% in rSkM1 and
by 31% in hH1a, but produced only minor changes in the half-points and slo
pe factors of their Q-V relationships. In contrast to measurements in contr
ol solutions, after modification by site-3 toxin the half-points of the G-V
and the Q-V relationships for rSkM1 Na+ channels demonstrated a concordanc
e similar to that for hH1a.
5. Q(max) vs. G(max) for rSkM1. and hH1a Na+ channels exhibited linear rela
tionships with almost identical slopes, as would be expected if the number
of electronic charges (e(-)) per channel was comparable.
6. We conclude that the faster kinetics in rSkM1 channels compared with hH1
a channels may arise from inherently faster rate transitions in skeletal mu
scle Na+ channels, and not from major differences in the voltage dependence
of the channel transitions.