Stimulation Of Sensory Neurons Research Articles

VIP as a mediator of hexamethonium-sensitive, atropine-resistant vasodilation in the cat tongue.

Electrical stimulation (10 V, 0.2 ms) of the chorda‐lingual nerve caused a biphasic vasodilatory response in the cat tongue with an initial phase which was most marked at low frequencies and a maintained phase which increased with frequency. Simultaneously, there was a VIP release as indicated by a marked increased VIP output from the tongue. VIP output increased with time of stimulation and was most pronounced at high frequencies. Atropine abolished the initial phase of vasodilation at low frequencies as well as reduced this phase at medium frequencies. At high frequency stimulation (15 Hz), the vasodilation was still somewhat reduced by atropine but in contrast to the cat submandibular salivary gland, the duration of the vasodilatory response did not increase after atropine. Furthermore, atropine did not increase VIP output from the tongue during nerve stimulation. Hexamethonium completely abolished VIP release as well as most of the vasodilation upon stimulation of the chorda‐lingual nerve. The remaining vasodilation may be due to antidromic stimulation of unmyelinated trigeminal sensory neurons, since it was present when using high threshold stimulation parameters (10 V, 5 ms). Local intra‐arterial infusion of acetylcholine or VIP caused a marked vasodilation of the tongue. Also substance P infusion induced a vasodilatory response. The response to acetylcholine was atropine sensitive, while the effects of VIP and substance P were atropine‐resistant. Combined infusions of VIP and acetylcholine had an additive effect on vasodilation. In conclusion, the present data suggest that low threshold chorda‐lingual nerve stimulation induced a release of both acetylcholine and VIP from postganglionic neurons in the tongue. The contribution by these two agents in the vasodilatory response may then depend upon time and frequency of stimulation. In contrast to the VIP nerves in the submandibular gland, no evidence suggests that VIP release from vascular nerves in the tongue is affected by atropine. High threshold stimulation also induces antidromic vasodilation possibly mediated via substance P release.

Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive sensory neurons.

Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive sensory neurons.

Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo.

The central terminals of small diameter primary sensory neurones associated with the transmission of noxious cutaneous stimuli are located predominantly in the superficial dorsal horn of the spinal cord1–3. Some of these neurones synthesize substance P (ref. 4) and transport this peptide to their central and peripheral terminals5–7. Substance P is released from the dorsal horn in vitro following potassium depolarization8,9; from spinal cord after electrical stimulation of dorsal roots10 and from dissociated sensory neurones grown in culture11. The iontophoretic application of substance P produces a long-lasting excitation of dorsal horn neurones that are also excited by noxious cutaneous stimuli12–14. One population of opiate receptors in the dorsal horn seems to be located on primary afferent terminals15–16; the release of substance P from primary sensory neurones is inhibited by opiates in vitro8,11. At present, however, there is no direct evidence that substance P is released from sensory neurones, in vivo, following activation of nociceptive afferents. We report here that substance P-like immunoreactivity is released from the mammalian spinal cord, in vivo, following chemical stimulation of sensory neurones with capsaicin and by the activation of high threshold peripheral afferents. Furthermore, release of substance P evoked by high intensity stimuli is completely inhibited by intrathecal morphine.

Attenuation in central neurons: its relationship to increased intracytoplasmic free calcium, calcium binding and memory storage.

A mechanism responsible for attenuation of dendritic spikes of nucleus reticularis gigantocellularis (NRG) origin was addressed. Stimulation of afferent neurons with pulses of 100 per sec frequency generated attenuation in specific neurons. Intrasomatic infusion of EGTA reversed the attenuation. The results suggest that attenuation results from intracytoplasmic accumulation of free Ca2+ due to differences in rate of Ca influx and Ca binding. This accumulation generates a concentration dependent prevention of Ca2+ (and Na+) influx that causes the attenuation. The free intracytoplasmic Ca2+ is removed mainly by binding on proteins and/or polypeptides, a mechanism that promotes memory storage.

Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica.

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.

Chronic diffuse interstitial fibrosis of the lungs.

Ca²⁺-dependent gene regulation controls many aspects of neuronal plasticity. Significant progress has been made toward understanding the roles of voltage- and ligand-gated Ca²⁺ channels in triggering specific transcriptional responses. In contrast, the functional importance of Ca²⁺ buffers and Ca²⁺ transporters in neuronal gene regulation is less clear despite their critical contribution to the spatiotemporal control of Ca²⁺ signals. Here we examined the role of mitochondrial Ca²⁺ uptake and release in regulating the Ca²⁺-dependent transcription factor NFAT (nuclear factor of activated T-cells), which has been implicated in synaptic plasticity, axonal growth, and neuronal survival. Intense stimulation of sensory neurons by action potentials or TRPV1 agonists induced rapid activation and nuclear import of NFAT. Nuclear translocation of NFAT was associated with a characteristic prolonged [Ca²⁺]_i elevation (plateau) that resulted from Ca²⁺ uptake by, and its subsequent release from, mitochondria. Measurements using a mitochondrial Ca²⁺ indicator, mtPericam, showed that this process recruited mitochondria throughout the cell body, including the perinuclear region. [Ca²⁺]_i levels attained during the plateau phase were similar to or higher than those required for NFAT activation (200–300 nm). The elimination of the [Ca²⁺]_i plateau by blocking either mitochondrial Ca²⁺ uptake via the uniporter or Ca²⁺ release via the mitochondrial Na⁺/Ca²⁺ exchanger strongly reduced nuclear import of NFAT. Furthermore, preventing Ca²⁺ mobilization via the mitochondrial Na⁺/Ca²⁺ exchanger diminished NFAT-mediated transcription. Collectively, these data implicate activity-induced Ca²⁺ uptake and prolonged release from mitochondria as a novel regulatory mechanism in neuronal excitation–transcription coupling.