Gating behaviour of sodium currents in adult mouse muscle recorded with an improved two-electrode voltage clamp

Non-technical summary Muscle contraction is triggered by the spread of an action potential along the fibre. The ionic current to generate the action potential is conducted through voltage-activated sodium channels, and mutations of these channels are known to cause several human muscle disorders. Mouse models have been created by introducing point mutations into the sodium channel gene. This achievement has created the need for a high-fidelity technique to record sodium currents from intact mouse muscle fibres. We have optimized a two-electrode voltage clamp, using sharp microelectrodes to preserve the myoplasmic contents. The voltage-dependent behaviour of sodium channel activation, inactivation and slow-inactivation were characterized. The voltage range for these gating behaviours was remarkably hyperpolarized, in comparison to studies in artificial expression systems. These results provide normative data for sodium channels natively expressed in mouse muscle and illustrate the need to modify model simulations of muscle excitability to account for the hyperpolarized shift.