Action potential generation in rat slow‐ and fast‐twitch muscles.

Abstract

1. In skeletal muscle fibres, voltage-gated sodium channels are concentrated at the neuromuscular junction. The effect of this accumulation of sodium channels on action potential generation was investigated in rat slow-and fast-twitch muscle fibres. 2. Intracellular microelectrodes were used to generate and record action potentials, from an imposed membrane potential of -75 and -90 mV, in junctional and extrajunctional regions of the muscle fibre. To identify junctional regions, preparations were incubated with 5 x 10-7 M d-tubocurarine (dTC) to block muscle contraction in response to nerve stimulation whilst allowing endplate potentials (EPPs) to be recorded. Injection of rectangular depolarizing current pulses initiated action potentials at the endplate with threshold values several millivolts lower than those generated elsewhere in the fibre. In addition, the maximum rate of rise of the action potential was greater at the endplate than in extrajunctional regions.3. In other muscles, neuromuscular transmission was partially blocked with dTC (2 x 10-7 M), such that repetitive nerve stimulation evoked action potentials and EPPs in the same fibre. The threshold of these nerve-evoked action potentials was approximately 50% lower than values derived from action potentials generated by current injection. 4. It is concluded that the threshold for action potential generation is significantly lower at the neuromuscular junction than in extrajunctional regions of skeletal muscle fibres. Furthermore, nerve-evoked current is more effective at generating an action potential than is injected current.

Physiological and ultrastructural features of human induced pluripotent and embryonic stem cell-derived skeletal myocytes in vitro

“…In both cell types, AP threshold and overshoot were comparable to those reported for cultured human primary myotubes from muscle biopsies (18,21), and for mammalian skeletal muscle, in general (22). AP kinetics vary with experimental conditions (temperature, protocols, etc.)…”

NMJ-morph reveals principal components of synaptic morphology influencing structure–function relationships at the neuromuscular junction

“…allowing quantal analyses to be acquired directly from recordings of endplate currents obtained using a two-electrode voltage clamp [41]). Wood & Slater [53,54] measured safety factor in this fashion by comparing the observed endplate current with that required to critically depolarize muscle fibres to the action potential firing threshold. They concluded that, once differences in the contribution of post-synaptic junctional folding were taken into account, the safety factor in rat soleus (a slow-twitch muscle) corresponded to about 3.5 times as much neurotransmitter released at an NMJ over the requirement to trigger muscle action potentials; but this was significantly lower than at NMJs in extensor digitorum longus (a fast-twitch muscle), where the safety factor was about 5.…”

Silencing rapsyn in vivo decreases acetylcholine receptors and augments sodium channels and secondary postsynaptic membrane folding

“…It has been suggested that the structure and molecular organization of the postsynaptic apparatus takes an excess of the released transmitter from the nerve, helping to ensure that every nerve impulse normally triggers a muscle action potential with a very small chance of failure. The concept of safety factor for neuromuscular transmission describes this excess (Martin, 1994;Wood and Slater, 1995, 1997, 2001. It is of interest that a modest reduction of rapsyn expression already causes substantial changes, showing that the amount of rapsyn is critically related to the AChR levels and to the structure of the endplate.…”