Activity-Dependent Modulation of Axonal Excitability in Unmyelinated Peripheral Rat Nerve Fibers by the 5-HT(3) Serotonin Receptor

Abstract

. Activity-dependent modulation of axonal excitability in unmyelinated peripheral rat nerve fibers by the 5-HT(3) serotonin receptor. J Neurophysiol 96: 2963-2971, 2006. First published September 6, 2006 doi:10.1152/jn.00716.2006. Activity-dependent fluctuations in axonal excitability and changes in interspike intervals modify the conduction of trains of action potentials in unmyelinated peripheral nerve fibers. During inflammation of a nerve trunk, long stretches of axons are exposed to inflammatory mediators such as 5-hydroxytryptamine . In the present study, we have tested the effects of m-chlorophenylbiguanide (mCPBG), an agonist at the 5-HT(3) serotonin receptor, on activity-and potential-dependent variations in membrane threshold and conduction velocity of unmyelinated C-fiber axons of isolated rat sural nerve segments. The increase in axonal excitability during application of mCPBG was much stronger at higher frequencies of action potentials and/or during axonal membrane hyperpolarization. The effects on the postspike recovery cycle also depended on the rate of stimulation. At an action potential frequency of 1 Hz or in hyperpolarized axons, mCPBG produced a loss of superexcitability. In contrast, at 0.33 Hz, a small increase in the postspike subexcitability was observed. Similar effects on excitability changes were found when latency instead of threshold was recorded, but only at higher action potential frequencies: at 1.8 Hz, mCPBG increased conduction velocity and reduced postspike supernormality. The latter effect would increase the interspike interval if pairs of action potentials were conducted along several cm in an inflamed nerve trunk. These data indicate that activation of axonal 5-HT(3) receptors not only enhances membrane excitability but also modulates action potential trains in unmyelinated, including nociceptive, nerve fibers at high impulse rates.

Pharmacological Manipulation of Immune-Induced Food Aversion in Rats

“…This might be an indication that, although not directly involved in allergic symptoms such as edema formation, 5-HT 3 receptor signaling is responsible for conveying to the brain at least part of the information derived from the allergic response in the gut. In accordance, we have previously reported that sensory C fibers, which are reported to express 5-HT 3 receptors [46] , are partly responsible for signaling allergic responses to the brain. Indeed, in a similar way, the destruction of C fibers by neonatal capsaicin did not abrogate the development of allergy-induced food aversion but significantly reduced its magnitude [3] .…”

Axon Physiology

“…They also determine axonal properties in mammalian axons. For instance, subtype 3 of the serotonin receptor (5-HT 3 ) modulates excitability of unmyelinated peripheral rat nerve fibers (316).…”

Conduction Failures in Rabbit Saphenous Nerve Unmyelinated Fibers

“…In an established model of painful diabetic neuropathy in the rat, a subset of C fibers demonstrated a marked hyper-responsiveness to mechanical stimuli and a greater mean CV [23] . Activation of the axonal receptor of 5-HT(3), an important inflammatory mediator, not only enhances membrane excitability but also modulates action potential trains in nociceptive C fibers at high impulse rates [39] . Based on these data we hypothesize that some pathological conditions, including inflammation, diabetic neuropathy and mutation in some specific genes, could perturb the adaptation properties by changing channel current balance and altering both the numbers and patterns of firing series, ultimately influencing perception.…”