The Universal ALS algorithm. An advisory statement by the Advanced Life Support Working Group of the International Liaison Committee on Resuscitation.
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Algorithms↗
Biomedical subjects
J Christenson
Publications and source records attributed to J Christenson.
Presence of low voltage activated calcium channels distinguishes touch from pressure sensory neurons in the lamprey spinal cord.
Touch (T) and pressure (P) primary sensory neurons (dorsal cells) in the lamprey spinal cord differ not only with regard to their mechanoreceptive properties but also in their membrane properties. Touch cells have a significantly shorter time delay to the spike onset on a rebound of a hyperpolarizing current pulse than the pressure cells. Different time constants and input resistances partially explain these findings but cannot fully account for the observed differences between T- and P-cells. A more detailed study of membrane properties was therefore required. 3-D reconstructions of dorsal cells reveal a round shape with few processes and thus that they are suitable for voltage clamp analysis. Voltage activated calcium channels with a low threshold were found in a subpopulation of dorsal cells after administration of tetrodotoxin and K+ channel antagonists. These channels were blocked by addition of Co2+. In the short latency T-cells Co2+ increased the latency under current clamp conditions, and inhibited the facilitatory effect on spike activation upon increased hyperpolarization. This effect of Co2+ was not observed in the long latency P-cells. It is likely that the presence of low voltage calcium channels in T-cells are responsible for the differences observed between T- and P-cells. Voltage activated calcium channels with a higher threshold were observed in dorsal cells of both types. These channels were blocked by Co2+ or cadmium. Late outward 'tail' currents were shown to include calcium dependent potassium channels.
Action Potentials↗
Possible morphological substrates for GABA-mediated presynaptic inhibition in the lamprey spinal cord.
Gamma-aminobutyric acid (GABA) neurons intrinsic to the lamprey spinal cord are known to modulate synaptic transmission from interneurons active during locomotion and from mechanosensory dorsal cells. Many of these physiological effects are presynaptic. To establish the morphological substrates for these axo-axonic interactions, an ultrastructural analysis was performed with an antiserum to fixed GABA. The GABA immunoreactivity (ir) was detected by postembedding peroxidase-antiperoxidase and immunogold techniques. GABA-ir terminals were found to make appositions with unlabelled axons located in the dorsal columns and in the ventrolateral aspect of the spinal cord. In the ventrolateral part of the cord, similar appositions between different GABA-ir terminals were also observed. The immunolabelled terminals contained spherical to pleomorphic synaptic vesicles, and also glycogen granules and dense core vesicles. In some cases, the fine structure of the contacts between immunogold-labelled terminals and unlabelled axons suggested a synaptic relationship. Such a relation was found in a relatively small proportion (2-3%) of the appositions studied. These specializations were always observed in close relation to an output synapse of the postsynaptic axon. It is suggested that the axo-axonal contacts described may provide an effective modulation of the synaptic transmission from axons in the lamprey spinal cord.
Animals↗
Subcellular distribution of serotonin in the lamprey spinal cord.
The subcellular distribution of serotonin (5-hydroxytryptamine; 5-HT) in the lamprey (Ichtyomyzon unicuspis, Lampetra fluviatilis) spinal cord was investigated by using ultracentrifugation on continuous density gradients combined with an electron microscopic analysis of the gradients and of immunostained tissue. Endogenous 5-HT was analyzed by high-performance liquid chromatography with electrochemical detection. After differential centrifugation, the highest levels of 5-HT were found in the particulate fractions. After ultracentrifugation of lysed synaptosomal fractions on continuous sucrose gradients and the subsequent sedimentation of the individual fractions, 5-HT showed a biphasic distribution in the gradient. The two peaks corresponded to 0.30-0.40 M and 0.85-1.05 M sucrose. Electron microscopy of intact tissue showed that some of the boutons were strongly immunoreactive to 5-HT with dense precipitates over large granular vesicles. The area around these large vesicles, however, also showed reaction product. Large granular vesicles could be clearly distinguished in the immunostained axonal varicosities. In tissue not processed for 5-HT immunoreactivity it was seen that the varicosities contained not only large dense-cored vesicles, but also small agranular vesicles. An electron microscopical analysis of the subcellular fractions revealed that the fraction corresponding to the "light" 5-HT peak contained numerous vesicular structures, which in most cases were electron lucent. In the "heavy" fractions, nerve ending particles containing vesicles of various sizes were observed. The results suggest that 5-HT in the lamprey spinal cord may be distributed in more than one subcellular compartment which, apart from the cytosol, possibly corresponds to small and large synaptic vesicles.
Animals↗
Co-localized GABA and somatostatin use different ionic mechanisms to hyperpolarize target neurons in the lamprey spinal cord.
gamma-Aminobutyric acid (GABA) and somatostatin are co-localized in cells close to the central canal in the lamprey. These cells project to the lateral margin of the spinal cord where they form a GABA and somatostatin containing plexus. Stretch receptor neurons (edge cells) are situated along the lateral margin of the spinal cord and their dendrites extend into the GABA and somatostatin containing plexus. To investigate whether GABA and/or somatostatin exert an affect on edge cells, these putative transmitters were applied from extracellular pipettes onto edge cells during intracellular recordings. Both GABA and somatostatin hyperpolarized the edge cells but through different ionic mechanisms. GABA activated a chloride current while somatostatin activated a current most likely carried by potassium which, however, could not be blocked by any of the conventional potassium blockers.
Animals↗
Putative GABAergic input to axons of spinal interneurons and primary sensory neurons in the lamprey spinal cord as shown by intracellular Lucifer yellow and GABA immunohistochemistry.
GABAergic phasic modulation of the membrane potential occurs in spinal interneurons during fictive locomotion in lamprey presumably indicating a presynaptic inhibition. GABA also modulates synaptic transmission from primary sensory neurons (dorsal cells) at a presynaptic site. From these findings GABA terminals would be expected to be in close contact with phasically modulated axons of spinal interneurons and/or dorsal cells and their axons. To test this supposition intracellular injections of Lucifer yellow into spinal interneurons or dorsal cells were combined with GABA immunohistochemistry. GABA-immunoreactive (ir) varicosities were found to be in close contact (less than 1 micron distance) with axons modulated during fictive locomotion as well as dorsal cell axons. Small GABA-ir bipolar neurons form processes, which are in close contact with the axons of dorsal cells.
Animals↗
Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey.
1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.
2-Amino-5-phosphonovalerate↗
Neuropeptide Y-immunoreactive spinal neurons make close appositions on axons of primary sensory afferents.
The dorsal cells in the lamprey are primary sensory neurons located in a parasagittal region of the spinal cord. In the same plane neuropeptide Y (NPY) immunoreactivity has been described. To investigate if the dorsal cells were in contact with NPY-immunoreactive (ir) fibers and cell bodies, intracellular injections of Lucifer yellow into identified dorsal cells were combined with NPY immunohistochemistry. NPY-ir varicosities were found to be in close apposition to both the descending and the ascending axon of dorsal cells. No NPY-ir boutons were seen in close contact with the dorsal cell bodies.
Afferent Pathways↗
5-hydroxytryptamine immunoreactive varicosities in the lamprey spinal cord have no synaptic specializations--an ultrastructural study.
The distribution and fine structure of 5-hydroxytryptamine (5-HT) immunoreactive cell bodies and axonal varicosities have been studied in the lamprey spinal cord, using the peroxidase-antiperoxidase (PAP) immunohistochemical technique and subsequent analysis of ultrathin serial sections. Immunostained cell bodies were found in the ventral spinal cord close to the central canal. Immunostained varicosities were found throughout the spinal cord with the highest density in the ventromedial plexus and the dorsal horn. Only large granular vesicles could be clearly distinguished in immunostained cell bodies and varicosities, but it was concluded based on a comparison with unstained normal tissue that these boutons also contained small, pleomorphic agranular vesicles. Immunoreactive varicosities were studied in the ventromedial plexus, the dorsal horn, the dorsal column, the dorsolateral and ventrolateral funiculi and the grey matter. No morphological differences could be observed between varicosities in the different loci. The varicosities were in no case seen to make synaptic contact with surrounding neuronal elements, even when followed through serial sections. Consequently, 5-HT released from boutons in all parts of the spinal cord could be expected to act on 5-HT receptors located on nearby as well as distant receptors.
Animals↗
Three types of GABA-immunoreactive cells in the lamprey spinal cord.
Polyclonal antisera raised against conjugated GABA were used to study the distribution of GABAergic neurons in the spinal cords of lampreys (Lampetra fluviatilis and Ichtyomyzon unicuspis) using immunofluorescence and peroxidase-antiperoxidase techniques. Three morphologically distinct types of GABA-immunoreactive (GABA-ir) cell bodies were observed, multipolar neurons in the lateral grey cell column, apparently bipolar cells in the ventral aspect of the dorsal horn, and small liquor-contacting cells surrounding the central canal. A high density of immunoreactive fibers of spinal origin were present in the lateral and ventral funiculi, whereas the dorsal column had a relatively low density. Dense GABA-ir plexuses were situated in the lateral spinal margin, and in the dorsal part of the dorsal horn. A chronic lesion of the rostral spinal cord did not result in any observable loss of GABA-ir fibers below or above the lesion, suggesting that the 3 types of segmental GABA-ir neurons are the main sources of the GABAergic innervation of the lamprey spinal cord.
Animals↗
Increase in endogenous 5-hydroxytryptamine levels modulates the central network underlying locomotion in the lamprey spinal cord.
To investigate the effects of an endogenous release of serotonin (5-HT) in the lamprey spinal cord, in vitro, the 5-HT uptake-blocker citalopram (1-10 microM) was added to the bathing solution. Samples taken from the physiological solution through high-performance liquid chromatography (HPLC) showed that 5-HT was released from the spinal cord. To study the effect of this endogenous release of 5-HT on the spinal network generating locomotion, 'fictive locomotion' was induced by bath application of N-methyl-D-aspartate (NMDA, 100 microM). It elicited a steady locomotor rhythm between 0.2 and 2.5 Hz. The effects of citalopram were the following: (1) the locomotor frequency slowed down, (2) the intensity of the ventral root bursts was increased and (3) the intersegmental phase lag was prolonged. The effects of citalopram and thus presumably of an endogenous release of 5-HT were similar to what has previously been observed during bath application of 5-HT. In the latter case the conditions are different, since all 5-HT receptors regardless of their location in relation to the 5-HT-containing boutons will be affected in a similar way.
Action Potentials↗
Mechanisms underlying the serotonergic modulation of the spinal circuitry for locomotion in lamprey.
The central nervous system of the lamprey contains serotonergic (5-hydroxytryptamine, 5-HT) neurones both in the spinal cord and in the brainstem. Endogenously released 5-HT from these systems modulates the pattern of fictive locomotion induced in the in vitro preparation; the burst rate is lowered and burst discharges become longer and of higher intensity. Local application of 5-HT, mimicking activation of the 5-HT systems, has a specific effect on the late phase of the afterhyperpolarization (AHP) in motoneurones and interneurones. 5-HT markedly reduces the amplitude of the late AHP without affecting passive membrane properties or the shape or threshold of the action potential. This 5-HT effect appears to result from a direct action on the calcium-dependent potassium channels underlying the late phase of the AHP. A reduction of the amplitude of the AHP will result in altered spike discharge characteristics, with potentiation of the response (discharge rate) to a given excitatory input in all neurones influenced by 5-HT. It is suggested that the modulatory effect of 5-HT on fictive locomotion can be attributed to its action on the late AHP and thereby to the potentiation of excitability in excitatory and inhibitory interneurones in the generator circuitry. This has been further corroborated in computer simulation studies of a network model, where the action of 5-HT was simulated by decreasing AHP amplitude, resulting in a slowing of the rhythm analogous to the effect demonstrated experimentally.
Animals↗
Effects of 5-hydroxytryptamine on the afterhyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons.
1. Local application of 5-hydroxytryptamine (5-HT) in the area in which a dense 5-HT plexus is located in the lamprey spinal cord leads to a marked depression of the late phase of the afterhyperpolarization (AHP) following the action potential. This effect was observed in motoneurons, premotor interneurons, and giant interneurons, whereas no effect was observed in the sensory dorsal cells and edge cells. 2. The late 5-HT sensitive phase of the AHP was increased in amplitude when calcium entry was enhanced during the prolongation of action potentials caused by tetraethylammonium (TEA). Conversely, a blockade of Ca2+ entry by manganese reduced the AHP amplitude, suggesting that a calcium-dependent current, most likely carried by potassium, underlies the late phase of the AHP in these cells, as is the case in many other types of neurons. 3. The late phase of the AHP could be depressed by 5-HT although no effects were exerted on either the resting input resistance or on the shape of the action potential in 54% of the cells. The membrane conductance increase associated with the late phase of the AHP was markedly attenuated by 5-HT application. 4. In voltage-clamp experiments, Na+ currents and most K+ currents were blocked by tetrodotoxin (TTX) and TEA, respectively. Under these conditions, voltage steps elicited a slow outward current, most likely representing a Ca2+-activated K+ current, which was depressed by 5-HT application. 5. 5-HT does not appear to reduce AHP amplitude by blocking the calcium entry occurring during the action potential. No evidence was obtained for an involvement of second messengers such as adenosine-3':5'-cyclic monophosphate (cAMP), guanosine-3':5'-cyclic monophosphate (cGMP), diacyglycerol, or arachidonic acid. The effect of 5-HT on the late AHP may be due to a direct action on the calcium-dependent potassium channels or on the intracellular handling of Ca2+ ions. 6. The amplitude reduction of the AHP has a profound influence on the spike frequency regulation of any given cell; the frequency of spikes evoked by a given excitatory stimulus is therefore markedly increased by application of 5-HT. 5-HT thus increases the "gain" of the input-output relation of interneurons and motoneurons responsible for generating the locomotor rhythm. In addition, 5-HT causes a prolongation of the depolarized plateau of the N-methyl-D-aspartate (NMDA) receptor-induced membrane potential oscillations, as expected from the 5-HT-induced effects on the Ca2+-activated K+ channels that contribute to the repolarization.
Action Potentials↗
The dorsal cell, one class of primary sensory neuron in the lamprey spinal cord. I. Touch, pressure but no nociception--a physiological study.
The dorsal cells in the lamprey spinal cord are primary sensory neurons. The cells were classified by Martin and Wickelgren in 1971 into 3 different groups, touch, pressure and nociceptive, according to their responses to mechanical stimulation of the skin. While confirming the presence of touch and pressure cells in the present study, we found no evidence for the existence of nociceptive spinal dorsal cells. Further we show that touch and pressure cells have different response latencies to a 40-ms hyperpolarizing current pulse. Measured from the end of the pulse to the initiation of the action potential, touch cells have a response latency shorter than 11 ms, whereas the pressure cells have a response latency longer than 11 ms.
Action Potentials↗
The dorsal cell, one class of primary sensory neuron in the lamprey spinal cord. II. A light- and electron microscopical study.
Dorsal cells, are primary sensory neurons located in the lamprey spinal cord. They are of two types conveying touch (T) and pressure (P) and they have an ascending and/or a descending axon which joins the dorsal column. Dorsal cells have no initial axon segment. In the electron microscope synaptic boutons with spherical synaptic vesicles were found in contact with the cell membrane of T-cells while no boutons have been observed on P-cells. No other morphological differences between T- and P-cells could be detected ultrastructurally or in the light microscope. No output synapses have been observed from the dorsal cell bodies or the small processes extending from the cell body.
Animals↗
The neuronal bases of locomotion in lamprey--in vitro studies of the brainstem-spinal cord.
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Animals↗
Single sensory neurons activate excitatory amino acid receptors in the lamprey spinal cord.
The effects of excitatory amino acid (EAA) antagonists were tested on sensory afferent excitation in the lamprey spinal cord. Paired intracellular recordings were made from mechanosensory neurons (dorsal cells) and second order sensory neurons (giant interneurons). Stimulation of individual dorsal cells evoked mono- and/or polysynaptic excitatory postsynaptic potentials (EPSPs) in giant interneurons. These EPSPs were depressed by the EAA antagonists cis-2,3-piperidine dicarboxylate and kynurenic acid. Small components of the synaptic potentials were due to electrical coupling since they were not depressed by EAA antagonists or by calcium-free solution. The N-methyl-D-aspartate antagonist 2-amino-5-phosphonovalerate did not depress short-latency EPSPs. Thus, mechanosensory neurons in the lamprey spinal cord activate EAA receptors (kainate/quisqualate receptors) on interneurons, via mixed chemical and electrical synapses.
Afferent Pathways↗
Compartmental pressure monitoring after arterial reconstruction lacks clinical relevance.
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Arteries↗