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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Stephen G Brohawn ◽  
Weiwei Wang ◽  
Annie Handler ◽  
Ernest B Campbell ◽  
Jürgen R Schwarz ◽  
...  
Keyword(s):  
Action Potential ◽  
Polyclonal Antibodies ◽  
Node Of Ranvier ◽  
Nerve Fibers ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Na Channel ◽  
Nodes Of Ranvier ◽  
Myelinated Nerve ◽  
Myelinated Nerve Fibers

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.

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

2019 ◽  
Author(s):  
Stephen G. Brohawn ◽  
Weiwei Wang ◽  
Jürgen R. Schwarz ◽  
Annie Handler ◽  
Ernest B. Campbell ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Polyclonal Antibodies ◽  
Node Of Ranvier ◽  
Nerve Fibers ◽  
Resting Membrane Potential ◽  
Myelinated Nerve ◽  
Myelinated Nerve Fibers ◽  
Behavioral Studies ◽  
Mechanosensitive Ion Channel

ABSTRACTTRAAK 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 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. Mechanical gating in TRAAK might serve a neuroprotective role by counteracting mechanically-induced ectopic action potentials. Alternatively, TRAAK may open in response to mechanical forces in the nodal membrane associated with depolarization during saltatory conduction and thereby contribute to repolarization of the node for subsequent spikes.

scholarly journals CHOLINESTERASE ACTIVITY OF NODAL AND INTERNODAL REGIONS OF MYELINATED NERVE FIBERS OF FROG

1967 ◽  
Vol 32 (3) ◽  
pp. 577-583 ◽  
Author(s):  
Miro Brzin ◽  
Wolf-D. Dettbarn
Keyword(s):  
Enzyme Activity ◽  
Esterase Activity ◽  
Cholinesterase Activity ◽  
Node Of Ranvier ◽  
Nerve Fibers ◽  
Selective Inhibitors ◽  
Myelinated Nerve ◽  
Myelinated Nerve Fibers ◽  
Significant Difference ◽  
Saltatory Conduction

The distribution of cholinesterase (Ch-esterase) in isolated myelinated fibers of the frog has been investigated. Quantitative microgasometric measurements have confirmed the previous histochemical observations. Both approaches indicate that in frog nerve fibers acetylcholinesterase (ACh-esterase) is the only or the predominant enzyme when selective inhibitors and different substrates are used: acetylcholine (ACh), butyrylcholine, and acetyl-B-methylcholine (Mecholyl). By means of the microgasometric technique, a significant difference in ACh-esterase activity between axons isolated from ventral (37.2 ± 1.7 µmole x 10-5 ACh/mm2/hr) and dorsal roots (2.0 ± 0.9 µmole x 10-5 ACh/mm2/hr) was found. In the region of the node of Ranvier the enzyme activity (50.4 ± 4.4 µmole x 10-5 ACh/mm2/hr) appears to be considerably higher than in the internodal area (36.6 ± 2.1 µmole x 10-5 ACh/mm2/hr). The findings are discussed in relation to the theory of saltatory conduction and the ACh system.

scholarly journals Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

1995 ◽  
Vol 105 (4) ◽  
pp. 485-505 ◽  
Author(s):  
M E Bräu ◽  
C Nau ◽  
G Hempelmann ◽  
W Vogel
Keyword(s):  
Local Anesthetics ◽  
Single Channel ◽  
Distribution Coefficients ◽  
Nerve Fibers ◽  
K Channel ◽  
Na Channel ◽  
Myelinated Nerve ◽  
Time Constants ◽  
Channel Inactivation ◽  
Ic50 Values

Effects of some local anesthetics were studied in patch clamp experiments on enzymatically demyelinated peripheral amphibian nerve fibers. Micromolar concentrations of external bupivacaine depolarized the excised membrane considerably. The flicker K+ channel was found to be the most sensitive ion channel to local anesthetics in this preparation. Half-maximum inhibiting concentrations (IC50) for extracellular application of bupivacaine, ropivacaine, etidocaine, mepivacaine, lidocaine, and QX-314 were 0.21, 4.2, 8.6, 56, 220, and > 10,000 microM, respectively. The corresponding concentration-effect curves could be fitted under the assumption of a 1:1 reaction. Application from the axoplasmic side resulted in clearly lower potencies with IC50 values of 2.1, 6.6, 16, 300, 1,200, and 1,250 microM, respectively. The log(IC50)-values of the local anesthetics linearly depended on the logarithm of their octanol:buffer distribution coefficients with two regression lines for the piperidine derivatives and the standard amino-amides indicating an inherently higher potency of the cyclic piperidine series. Amide-linked local anesthetics did not impair the amplitude of the single-channel current but prolonged the time of the channel to be in the closed state derived as time constants tau c from closed-time histograms. With etidocaine and lidocaine tau c was 133 and 7.2 ms, and proved to be independent of concentration. With the most potent bupivacaine time constants of wash in and wash out were 1.8 and 5.2 s for 600 nM bupivacaine. After lowering the extracellular pH from 7.4 to 6.6, externally applied bupivacaine showed a reduced potency, whereas at higher pH of 8.2 the block was slightly enhanced. Intracellular pH of 6.4, 7.2, 8.0 had almost no effect on internal bupivacaine block. It is concluded that local anesthetics block the flicker K+ channel by impeding its gating but not its conductance. The slow blocker bupivacaine and the fast blocker lidocaine compete for the same receptor. Lipophilic interactions are of importance for blockade but besides a hydrophobic pathway, there exists also a hydrophilic pathway to the binding site which could only be reached from the cytoplasmic side of the membrane. Under physiological conditions, blockade of the flicker K+ channel which is more sensitive to bupivacaine than the Na+ channel might lead via membrane depolarization and the resulting sodium channel inactivation to a pronounced block of conduction in thin fibers.

scholarly journals THE SUBMICROSCOPIC ORGANIZATION OF AXON MATERIAL ISOLATED FROM MYELIN NERVE FIBERS

1953 ◽  
Vol 98 (3) ◽  
pp. 269-276 ◽  
Author(s):  
E. De Robertis ◽  
C. M. Franchi
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Phase Contrast ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Myelinated Nerve Fibers ◽  
Dense Granules ◽  
Small Clusters ◽  
Membranous Material ◽  
The Way

A technique has been developed for the extrusion of axon material from myelinated nerve fibers. This material is then compressed and prepared for observation with the electron microscope. All the stages of preparation and purification of the axon material can be checked microscopically and in the present paper they are illustrated with phase contrast photomicrographs. Observation with the electron microscope of the compressed axons showed the presence of the following components: granules, fibrils, and a membranous material. Only the larger granules could be seen with the ordinary microscope. A considerable number of dense granules were observed. Of these the largest resemble typical mitochondria of 250 mµ by 900 mµ. In addition rows or small clusters of dense granules ranging in diameter from 250 to 90 mµ were present. In several specimens fragments of a membrane 120 to 140 A thick and intimately connected with the axon were found. The entire axon appeared to be constituted of a large bundle of parallel tightly packed fibrils among which the granules are interspersed. The fibrils are of indefinite length and generally smooth. They are rather labile structures, less resistant in the rat than in the toad nerve. They varied between 100 and 400 A in diameter and in some cases disintegrated into very fine filaments (less than 100 A thick). The significance is discussed of the submicroscopic structures revealed by electron microscopy of the material prepared in the way described.

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