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Thurman M. Wheeler, John D. Lueck, Maurice S. Swanson, Robert T. Dirksen, Charles A. Thornton
Published in Volume 117, Issue 12
J Clin Invest. 2007; 117(12):3952–3957 doi:10.1172/JCI33355
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Figure 4
Antisense morpholino rescues ClC-1 channel function and reverses myotonia in skeletal muscle of HSALR mice.

(A) Representative ClC-1 currents obtained from FDB fibers isolated from HSALR mice electroporated with either invert (left) or antisense (middle) morpholino and WT mice electroporated with antisense morpholino (right). The dashed lines represent the 0 current level. Capacitative currents recorded from each fiber are shown in the inset of each panel (scale bars: vertical, 3 nA; horizontal, 4 ms). Superimposed traces (solid lines) of normalized ClC-1 current deactivation at –100 mV in FDB fibers obtained from invert- (circles) and antisense-treated (squares) HSALR mice and antisense-treated WT mice (triangles) fit with a second-order exponential are shown in the inset to the left panel. Note that accelerated ClC-1 deactivation kinetics of FDB fibers obtained from HSALR mice are normalized only following treatment with antisense morpholino. (B) Membrane potential (Vm) dependence of average instantaneous ClC-1 current density recorded from FDB fibers of 16- to 18-day-old WT mice treated with invert morpholino (n = 11), WT mice treated with antisense morpholino (n = 10), HSALR mice treated with invert morpholino (n = 12), and HSALR mice treated with antisense morpholino (n = 16). (C) Average relative Po-Vm curves for the same experiments shown in B. Smooth curves through each data set were generated using a modified Boltzmann equation (10). (D) Average relative contribution of the fast (Af/Atotal), slow (As/Atotal), and nondeactivating (C/Atotal) components of ClC-1 current deactivation elicited from a voltage step to –100 mV for the same experiments shown in B. Mean ± SEM; *P < 0.05 invert-treated HSALR fibers compared with each of the other experimental conditions; t test. Myotonia was significantly reduced 3 (E) and 8 (F) weeks following injection of antisense morpholino. Mean ± SD; n = 3–7 per group. Antisense morpholino was injected into one TA; invert morpholino was injected into the contralateral TA; and gastrocnemius muscle served as an untreated control. **P < 0.0001 for antisense versus invert-treated control; ANOVA.