Na+ current densities and voltage dependence in human intercostal muscle fibres.

Abstract

SUMMARY1. Voltage-clamp Na+ currents (INa) were studied in human intercostal muscle fibres using the loose-patch-clamp technique.2. The fibres could be divided into two groups based upon the properties of INa* The two groups of fibres were called type 1 and type 2.

Fiber Types in Mammalian Skeletal Muscles

“…Expression of Nav 1.5 is restricted to immature and denervated muscles (389), while Nav 1.4 is expressed in adult muscles both in slow and fast fibers. Na channel density is two to three times higher in fast than in slow fibers in humans (673) as in other mammals (125,185). This is consistently supported by evidence obtained in electrophysiological studies as well as in saxitonin binding experiments (317).…”

“…Very high concentrations of channels are present in the membrane in the depths of the folds under the NMJ (125,223), with the likely goal to amplify the effect of the released transmitter or to reduce the threshold for nerve-evoked action potential (743). The gradient in Na current moving away from the endplate is much lower in slow fibers (673).…”

“…Importantly, inactivation, i.e., the transient decrease of Na conductance which follows a change in membrane potential, has two components: slow inactivation has a time constant in the order of 20 -30 s (736), whereas fast inactivation is much faster (time constant in the order of 0.1-1 ms) and occurs at less negative potentials. Comparing fast and slow fibers, fast inactivation acts at potentials less negative in slow (V h1/2 ϾϪ65 mV) than in fast fibers (V h1/2 ϽϪ65 mV), and the same is true for slow inactivation (V s1/2 ϷϪ70 mV in slow and ϷϪ95 mV in fast fibers) (185,671,673). The molecular basis of such kinetic diversity among fiber types is still uncertain since, as stated above, only one isoform of the pore forming ␣ subunit and one isoform of the auxiliary ␤ subunit are expressed in both slow and fast adult skeletal muscle fibers.…”

“…The resting membrane potential is more negative in fast than slow fibers in rat (842) and human muscles (670,673), with potential ranges between Ϫ80 and Ϫ85 mV in slow fibers and between Ϫ90 and Ϫ95 mV in fast fibers. The membrane capacitance per unit area is similar in fast and slow fibers: for example, values of 3.82 versus 3.76 F/cm 2 have been calculated in slow and fast human muscle fibers, respectively (673). In contrast, the membrane resistance per unit area is lower in fast than slow fibers (for example, 358 ⍀/cm 2 in fast rat fibers versus 588 ⍀/cm 2 in slow fibers), and the difference has been attributed to a greater expression of chloride channels in fast muscle fibers (see below).…”

Myasthenic syndrome caused by plectinopathy

“…Thus loss of cytoskeletal support of the junctional folds due to the plectin deficiency, as depicted in figure e-3, readily explains the progressive destruction of the folds. Destruction of junctional folds decreases the density or eliminates the voltage-gated Na ϩ channels which are concentrated in troughs between the folds 35,36 and this increases the threshold for action potential generation. 37 Destruction of the folds also decreases the input resistance of the postsynaptic membrane and thereby the amplitude of synaptic potential.…”