The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier.

TRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in what is likely an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the leak K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. We speculate on why nodes of Ranvier contain a mechanosensitive K+ channel

Sodium channel inactivation kinetics of rat sensory and motor nerve fibres and their modulation by glutathione

Na+ channel currents of rat motor and sensory nerve fibres were studied with the patch-clamp technique on enzymatically demyelinated axons. Differences between motor and sensory fibres in multi-channel inactivation kinetics and the gating of late single-channel currents were investigated. In the axon-attached mode, inactivation of multi-channel Na+ currents in sensory axons was best fitted with a single time constant while for motor axons two time constants were needed. Late single-channel currents in sensory axons were characterized by short openings whereas motor axons exhibited additional long single-channel openings. In contrast, in excised, inside-out membrane patches, no differences between motor and sensory fibres were found: in both types of fibre inactivation of multi-channel Na+ currents proceeded with two time constants and late single-channel currents showed short and long openings. After application of the reducing agent glutathione to the cytoplasmic side of excised inside-out patches, inactivation of Na+ currents in both motor and sensory fibres proceeded with a single, fast exponential time constant and late currents appeared with short openings only. These data indicate that the axonal metabolism may contribute to the different inactivation kinetics of Na+ currents in motor and sensory nerve fibres

Modelling selective activation of small myelinated nerve fibres using a monopolar point electrode

The aim of this study is to investigate theoretically the possibility for activation of small myelinated nerve fibres without activating larger ones when stimulating a nerve fibre bundle using a monopolar point electrode. Therefore, the sensitivity of excitation and blocking threshold currents of nerve fibres to fibre diameter, electrode-fibre distance and pulse duration has been simulated by a computer model. A simple infinite, homogeneous volume conductor and a cathodal point source were used in combination with a model representing the electrical properties of a myelinated nerve fibre. The results show that selective activation of small myelinated fibres may be possible in a region at some distance from the electrode

Membrane properties of Ranvier nodes from South American toads frogs (Bufo marinus ictericus and Leptodactylus ocellatus)

Estudaram-se propriedades eletrofisiológicas de membranas excitáveis em algusn anfíbios do Brasil. O presente trabalho refere-se aos resultados obtidos em nódulos de Ranvier de fibras motoras e sensoriais isoladas de Bufo marinus ictericus e Leptodactylus ocellatus. Empregou-se o método desenvolvido por Nonner (1969)

Some factors affecting nerve conduction

In the past compound action potential recording has been widely employed to investigate patterns of nerve conduction block. This technique, however, has a number of methodological drawbacks which do not apply to the unitary action potential recording technique. In this thesis unitary potentials have been recording during a number of types of nerve block to gain a better understanding of the underlying events. It was found that 250 mmHg of pressure applied to the isolated frog nerve generated a differential block of fast myelinated axons as a result of nerve fibre deformation. However, nerve ischaemia (studied in the cat sciatic nerve) was found to have the opposite effect, generating a differential block of slow axons. Conduction block induced by compression in vivo was found to have a similar pattern to that induced by ischaemia when of the order associated with the clinically prevalent carpel tunnel syndrome. More extreme compression however, of the order associated with clinically acute compression lesions, was found to differentially affect fast axons, suggesting that block is due to physical trauma under these conditions. Experiments were also performed to evaluate how the structure-function relationship of the frog myelinated axon influences the axons' response to changes in ionic environment. It was found that perfusion of frog myelinated axons with a high potassium concentration induced slowing in action potential conduction velocity over a diphasic time course, apparently due to potassium diffusing into both the perinodal and the periaxonal compartments. Potassium diffusion into the periaxonal space was found to have profound effects upon nerve conduction, while the slow evolution of these effects indicates effective potassium ion homeostasis beneath the myelin sheath. In contrast to high potassium perfusion, low sodium perfusion produced simple monotonic changes in conduction velocity, affecting the slowest group of axons to the greater extent. This confirms an earlier theoretical prediction that small myelinated axons have a low safety factor and may explain the differential action of local anaesthetics. An assessment was also made of the use of compound action potential recording as a technique to investigate changes in nerve conduction. This showed that compound action potentials are a valuable tool for evaluating qualitative changes in nerve conduction, but are not appropriate for demonstrating the specific block of a group of axons