Axon-glia interactions modulate axonal excitability in mammalian unmyelinated nerves.

A period of electrical activity in unmyelinated nerve fibers is followed by a post-tetanic hyperpolarization (PTH), generated by the hyperactivity of the electrogenic Na(+)-K(+) pump. In order to protect the membrane potential against these strong hyperpolarizations, different types of axonal inward currents are activated during the PTH. We investigated in the rabbit vagus nerve one of these currents, which was activated by carbamylcholine (CCh).

Inhibition of the I(h) current in isolated peripheral nerve: a novel mode of peripheral antinociception?

Although the alpha2-adrenergic agonist clonidine has been shown to promote peripheral antinociception, its mechanism of action has not yet been clearly elucidated. By the use of the sucrose-gap method, we have shown that in C fibers of the rabbit vagus nerve, clonidine at micromolar concentrations enhances activity-dependent hyperpolarizations generated by the Na+-K+ pump during and after repetitive stimulation. Similar results were obtained with 10 microM of ZD 7288, a specific blocker of the hyperpolarization-activated cation current (I(h)) and with 2 mM of Ba2+ that blocks the inwardly rectifying potassium current (I(KIR)).

Glia-axon interactions and the regulation of the extracellular K+ in the peripheral nerve.

Changes in membrane potential of both axons and Schwann cells were measured simultaneously during electrical activity and during the period of recovery in the rabbit vagus nerve by the use of the sucrose-gap apparatus. During low-frequency stimulation (0.5-1 Hz) the preparation developed a ouabain-sensitive hyperpolarization.

Mechanism of antinociceptive action of clonidine in nonmyelinated nerve fibres.

Despite a large body of clinical evidence in favour of a local anesthetic effect of clonidine, the underlying mechanism has not yet been elucidated. In this study we have used the sucrose-gap method to measure the effects of clonidine on the electrophysiological properties of nonmyelinated nerve fibers in the rabbit vagus nerve. The results showed that clonidine enhanced the hyperpolarizing and reduced the depolarizing afterpotential that follow compound action potentials during electrical activity.

Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve.

Changes in membrane potential and potassium concentration in the extracellular space ([K+]e) of rabbit vagus nerve were measured simultaneously during electrical activity and during the period of recovery using a modified sucrose-gap method and potassium-sensitive microelectrodes. After stimulation for 15 s at 15 Hz the main activity-induced increase in [K+]e reached 16.9 mM.

Lactate is released and taken up by isolated rabbit vagus nerve during aerobic metabolism.

To determine if lactate is produced during aerobic metabolism in peripheral nerve, we incubated pieces of rabbit vagus nerve in oxygenated solution containing D-[U-14C]glucose while stimulating electrically. After 30 min, nearly all the radioactivity in metabolites in the nerve was in lactate, glucose 6-phosphate, glutamate, and aspartate. Much lactate was released to the bath: 8.

Uptake of potassium by nonmyelinating Schwann cells induced by axonal activity.

1. The electrophysiological properties of the rabbit vagus nerve (membrane potential, compound action potentials, and afterpotentials) and potassium accumulation were measured simultaneously during low-frequency stimulation (LFS) (0.5 and 1 Hz) by using a modified sucrose-gap apparatus and potassium-sensitive microelectrodes (KSM).

Long-range intercellular signalling in glial cells of the peripheral nerve.

Schwann cells are considered to be electrically silent satellite cells surrounding axons, although they exhibit ionic channels, some of which are similar to those employed by axons for the generation and transmission of nerve impulses. Here, we show that Schwann cells generate, in response to a short and gentle electrical stimulus, a long-lasting depolarizing potential, slowly propagating along the Schwann cell synsitium. This electrical signal, which in situ might be generated by the Schwann cells in response to the axonal electrical activity, constitutes in the peripheral glia a novel form of long-range intercellular signalling, which may be involved in the regulation and modulation of the axonal excitability.

Hyperpolarizing afterpotentials in C fibers and local anesthetic effects of clonidine and lidocaine.

Effects of clonidine and lidocaine on the hyperpolarizing after-potential (HAP) and frequency-dependent block in C fibers were examined on desheathed rabbit vagus nerves, using the sucrose gap technique. A single action potential (AP) was followed by a fast and a slow HAP. Clonidine, at concentrations from 0.

Clonidine enhances the effects of lidocaine on C-fiber action potential.

We examined local anesthetic effects of clonidine and its interaction with lidocaine with regard to tonic inhibition of the C-fiber action potential (AP) on the isolated, desheathed rabbit vagus nerve by the sucrose gap method. Clonidine and lidocaine at 500 microM concentrations caused a comparable degree of C-fiber inhibition, corresponding to an AP area under the curve of 75.8% +/- 9.

After potentials in nonmyelinated nerve fibers.

1. The sucrose-gap technique was employed to examine the different types of after potentials that follow, in desheathed rabbit vagus nerves, a single action potential (AP) elicited by a short (0.4 ms) supramaximal depolarizing pulse.

Calcium efflux and intracellular exchangeable calcium in mammalian nonmyelinated nerve fibers.

Calcium efflux was measured in desheathed rabbit vagus nerves loaded with 45Ca2+. The effects of extracellular calcium, sodium, phosphate, potassium and lanthanum ions on the calcium efflux were investigated and the distribution of intracellular calcium determined by kinetic analysis of 45Ca2+ efflux profiles. The 45Ca2+ desaturation curve can be adequately described by three exponential terms.

Continuous measurement of calcium influx in mammalian nonmyelinated nerve fibers: effects of Nao, Cao, and electrical activity.

A new technique for continuous monitoring of the cellular calcium was developed and used for studying the effects of external and internal Na (Nao and Nai), external Ca (Cao), Ca ionophore A23187, and electrical activity on membrane-bound and intracellular Ca in mammalian nonmyelinated nerve fibers. Increasing Cao increased both the membrane-bound and the intracellular Ca. Lowering Nao increased the membrane-bound fraction of Ca indicating that lack of Nao enhanced the capacity of the plasma membrane to bind Ca, and produced an increase of the internal Ca pool.

Involvement of intracellular calcium in the phosphate efflux from mammalian nonmyelinated nerve fibers.

Phosphate efflux was measured as the fractional rate of loss of radioactivity from desheathed rabbit vagus nerves after loading with radiophosphate . The effects of strategies designed to increase intracellular calcium were investigated. At the same time, the exchangeable calcium content was measured using 45Ca.

Effects of calcium and lanthanum on phosphate efflux from nonmyelinated nerve fibers.

Phosphate efflux was measured as the fractional rate of loss of radioactivity from rabbit vagus loaded with radiophosphate. The effects of changes in extracellular calcium and of lanthanum have been investigated. In Locke solution with normal, 0.

The correction factors for sucrose gap measurements and their practical applications.

The distribution of extracellular and intracellular potential in the sucrose gap apparatus, previously established for a single fiber using the cable equations for a core conductor model (Jirounek and Straub, Biophys. J., 11:1, 1971), is obtained for a multifiber preparation.

Efflux of inorganic phosphate from mammalian non-myelinated nerve fibres.

1. Uptake and release of radiophosphate were measured in desheathed rabbit vagus nerve. 2.

Sodium-dependent influx of orthophosphate in mammalian non-myelinated nerve.

1. The rate of uptake of radiophosphate was measured in desheathed vagus nerves of rabbits mounted in an apparatus where the incubating solution flowed along the preparation. 2.

Uptake of orthophosphate by rabbit vagus nerve fibres.

1. The uptake of orthophosphate and its incorporation into ATP, ADP, and creatine phosphate (CrP) were studied in desheathed rabbit vagus nerve. 2.