Diversity of sympathetic vasoconstrictor pathways and their plasticity after spinal cord injury

Sympathetic vasoconstrictor pathways pass through paravertebral ganglia carrying ongoing and reflex activity arising within the central nervous system to their vascular targets. The pattern of reflex activity is selective for particular vascular beds and appropriate for the physiological outcome (vasoconstriction or vasodilation). The preganglionic signals are distributed to most postganglionic neurones in ganglia via synapses that are always suprathreshold for action potential initiation (like skeletal neuromuscular junctions). Most postganglionic neurones receive only one of these “strong” inputs, other preganglionic connections being ineffective. Pre- and postganglionic neurones discharge normally at frequencies of 0.5–1 Hz and maximally in short bursts at <10 Hz. Animal experiments have revealed unexpected changes in these pathways following spinal cord injury. (1) After destruction of preganglionic neurones or axons, surviving terminals in ganglia sprout and rapidly re-establish strong connections, probably even to inappropriate postganglionic neurones. This could explain aberrant reflexes after spinal cord injury. (2) Cutaneous (tail) and splanchnic (mesenteric) arteries taken from below a spinal transection show dramatically enhanced responses in vitro to norepinephrine released from perivascular nerves. However the mechanisms that are modified differ between the two vessels, being mostly postjunctional in the tail artery and mostly prejunctional in the mesenteric artery. The changes are mimicked when postganglionic neurones are silenced by removal of their preganglionic input. Whether or not other arteries are also hyperresponsive to reflex activation, these observations suggest that the greatest contribution to raised peripheral resistance in autonomic dysreflexia follows the modifications of neurovascular transmission

A Slow Voltage-Activated Potassium Current in Rat Vagal Neurons

Potassium currents play a key role in controlling the excitability of neurons. In this paper we describe the properties of a novel voltage-activated potassium current in neurons of the rat dorsal motor nucleus of the vagus (DMV). Intracellular recordings were made from Dmv neurons in transverse slices of the medulla. Under voltage clamp, depolarization of these neurons from hyperpolarized membrane potentials (more negative than - 80 mV) activated two transient outward currents. One had fast kinetics and had properties similar to A-currents. The other current had an activation threshold of around - 95 mV (from a holding potential - 110 mV) and inactivated with a time constant of about 3 s. It had a reversal potential close to the potassium equilibrium potential. This current was not calcium dependent and was not blocked by 4-aminopyridine (5 mM), catechol (5 mM) or tetraethylammonium (20 mM). It was completely inactivated at the resting membrane potential. This current therefore represents a new type of voltage-activated potassium current. It is suggested that this current might act as a brake to repetitive firing when the neuron is depolarized from membrane potentials negative to the resting potential

Membrane-Properties and Synaptic Potentials in Rat Sympathetic Preganglionic Neurons Studied in Horizontal Spinal-Cord Slices In-Vitro

Intracellular recordings were made from neurons in the intermediolateral column and adjacent white matter in horizontal slices of upper thoracic spinal cord from rats aged 21-28 days. Membrane properties were studied in the presence of picrotoxin (100 mu M) to block ongoing inhibitory synaptic potentials. 37 neurons were identified as sympathetic preganglionic neurons (SPNs) by their electrical behaviour, anatomical location and/or morphology. SPNs had resting potentials of - 57 +/- 2 mV and input resistances of 254 +/- 31 M Omega(n = 14). Following a hyperpolarising voltage step, a transient outward current was activated which had a lime constant of decay of approx. 400 ms. The inflection in the repolarising phase of the action potential and the following prolonged AHP were both abolished by Cd2+ (50 mu M). The current underlying the AHP had two components with kinetic properties similar to the two calcium-activated potassium conductances, gKCa1, and gKCa2, characterized in other autonomic neurons. Noradrenaline (10-100 mu M) caused a small depolarization and blocked the calcium component of the action potential suppressing the AHP. This revealed an afterdepolarization (ADP) with an underlying inward current with a decay time constant of approx. 150 ms. All effects of noradrenaline were blocked by phentolamine (10 mu M). Graded stimulation of the lateral funiculus 0.5-1 mm rostral to the recording site evoked in all cells monosynaptic fast excitatory synaptic potentials (fEPSPs) which were graded in amplitude. fEPSPs decayed with a time constant identical to the cell input time constant and were reduced in amplitude by CNQX (10-20 mu M). In 7 cells, higher stimulus voltages elicited slow EPSPs with a time to peak of 1.1 +/- 0.1 s and a half decay of 2.8 +/- 0.3 s (n = 7) which were not reduced by alpha-adrenoceptor antagonists. The AHP was not blocked when the action potential was initiated during the slow EPSP. We conclude that excitatory bulbospinal inputs to SPNs involve at least one fast transmitter which is likely to be glutamate and one slow transmitter which is not noradrenaline

Calcium Induced Calcium Release Is Involved in the Afterhyperpolarization in One Class of Guinea-Pig Sympathetic Neuron

The mechanisms underlying two potassium conductances which are activated by Ca2+ influx during the action potential in sympathetic prevertebral neurones of guinea pigs have been investigated pharmacologically. One Ca-activated K+ conductance, which is present in all mammalian sympathetic postganglionic neurones, is maximal after the action potential and decays exponentially with a time constant of about 130 ms; this conductance was inhibited by apamin (50-100 nM) consistent with the involvement of SK channels. A second Ca-activated K+ conductance with much slower kinetics is present in a large subpopulation of coeliac neurones. This conductance was resistant to apamin but markedly inhibited by application of ryanodine (5-20 muM), suggesting that Ca2+ influx during the action potential triggers release of Ca2+ from intracellular stores which in turn activates a different class of K+ channel. Noradrenaline (100 muM) depressed the second K+ conductance selectively

Are there functional P2X receptors on cell bodies in intact dorsal root ganglia of rats?

P2X purinoceptors have been suggested to participate in transduction of painful stimuli in nociceptive neurons. In the current experiments, ATP (1-10 mM), alpha,beta-methylene-ATP (10-30 mu M) and capsaicin (10 nM-1 mu M) were applied to neurons impaled with high resistance microelectrodes in rat dorsal root ganglia (L4 and L5) isolated in vitro together with the sciatic nerve and dorsal roots. The agonists were either bath applied or focally applied using a picospritzer. GABA (100 mu M) and 40-80 mM K+ solutions gave brisk responses when applied by either technique. Only three of 22 neurons with slowly conducting axons (C cells) showed evidence of P2X-purinoceptor-mediated responses. Only two of 13 cells which responded to capsaicin (putative nociceptors), and none of 29 cells with rapidly conducting axons (A cells), responded to the purinergic agonists. When acutely dissociated dorsal root ganglion cells were studied using patch-clamp techniques, all but four of 30 cells of all sizes responded with an inward current to either ATP or alpha,beta-methylene-ATP (both 100 mu M). Our data suggest that few sensory cell bodies in intact dorsal root ganglia express functional purinoceptors. (C) 1998 IBRO. Published by Elsevier Science Ltd