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M Randić

Publications and source records attributed to M Randić.

At least 55 records · Page 3Linked to original sources
PubMed1985

The acute and chronic effects of capsaicin on slow excitatory transmission in rat dorsal horn.

The acute and chronic effects of capsaicin on rat spinal dorsal horn neurons and the excitatory transmission in the dorsal horn were investigated by means of intracellular recording techniques in the spinal cord slice preparation. Bath application of capsaicin (1-2 X 10(-5) M) produced in a majority of cells a prolonged depolarization associated with an increase in synaptic activity and intense neuronal discharges. During and immediately following the capsaicin depolarization, repetitive stimulation of a dorsal root failed to elicit the slow depolarization. After neonatal capsaicin treatment the proportion of dorsal horn neurons exhibiting the slow excitatory transmission was markedly reduced, however, the fast excitatory postsynaptic potentials were present in all examined cells. In addition, the proportion and sensitivity of the cells responding with a slow depolarization to substance P increased.

Animals↗
PubMed1985

Graph theoretical approach to structure-activity studies: search for optimal antitumor compounds.

An approach based on graph theoretical methods for searching the most potent drug among numerous candidate structures is outlined. First, we identify the strategic fragment and describe it by suitable graph theoretical invariants. We have adopted path numbers derived from suitably weighted bonds as basic invariants. Similarity among structures is quantitatively derived from similarity and differences in atomic path numbers for the strategic fragment. The approach is illustrated on a selection of antitumor phenyldialkyltriazenes for which log(1/C) are known. By starting the search with an unsubstituted parent compound, in few steps we located 1-(4-NHCOCH3-Phenyl)-3,3-dialkyltriazene as the most potent drug among those considered.

Antineoplastic Agents↗
PubMed1984

Slow excitatory transmission in rat dorsal horn: possible mediation by peptides.

Repetitive stimulation of a dorsal root elicited a slow depolarization in about half of the dorsal horn neurons examined in the rat spinal cord slice preparation. The response was markedly depressed or abolished in the presence of substance P, substance P antagonists and capsaicin. In some dorsal horn neurons a slow hyperpolarization was also observed.

Animals↗
PubMed1984

Ascending spinal axons that signal the position of the hindlimbs under static conditions: location and receptor input.

Psychophysical experiments have shown that signals from slowly adapting subcutaneous receptors are used to sense limb position under static conditions (i.e., when the joints are stationary). The ascending collaterals of the slowly adapting primary sensory neurons supplying the deep tissues of the hindlimb do not project to the brain via the fasciculus gracilis. In experiments on cats, we have found a population of axons in the lateral fasciculus that signal the position of the ipsilateral hindlimb with a slowly adapting discharge. In the lower thoracic cord these fibers lie between the spinocervical tract and the ventral roots. Although plentiful in the lower thoracic cord, they are sparse or absent below L3. In addition, a few position signaling axons with crossed input were found in the ventral part of the lateral white matter and in the ventral columns. Since the clinical evidence suggests that the spinal pathway for position sense is uncrossed, we propose that information used for conscious judgments of limb position when the joints are stationary initially ascends via the dorsal columns and then relays to the lateral fasciculus on the same side. These slowly adapting signals also may be used to judge limb position when the joints are moving. To determine whether this slowly adapting discharge originates from muscle or joint receptors, the tendons crossing the ankle joint were exposed but left in continuity and then pulled on while the joint was stationary. In this way individual lateral fascicular axons that signaled ankle flexion, extension, abduction or adduction could be shown to receive a strong excitatory input from muscle receptors. After the muscle tendons crossing the ankle joint were cut, tract fibers signaling ankle flexion, extension, abduction or adduction could no longer be found in this portion of the spinal white matter. Axons signaling clockwise or counterclockwise twist of the ankle were reduced in number but a few were still present. These results suggest that muscle receptors provide the predominant signal used to sense ankle flexion, extension, abduction and adduction and that receptors in articular tissues may signal ankle twist.

Afferent Pathways↗
PubMed1984

Signaling of ankle joint position by receptors in different muscles.

Plots were made of multiunit activity versus ankle joint position for receptors in each of the 12 muscles crossing the cat ankle joint, except peroneus tertius, by recording from populations of afferent fibers in muscle nerves. The discharge was measured 15 or 30 sec after terminating the movements that altered the position of the joint. These recordings were dominated by large-spike activity that would be expected to originate mainly from primary spindle endings. Seven of the 12 muscles also cross other joints. Their responses at a given ankle joint position were so altered by changes in the position of the knee or toe joints that they could not reliably signal the position of the ankle joint. As judged from multiunit recording, receptors in each of the five muscles specific to the ankle joint were influenced by more than one axis of ankle joint displacement. Single-unit recording from dorsal root filaments was used to determine whether primary or secondary spindle receptors in soleus and tibialis anterior could selectively signal one axis of ankle joint rotation. Individual soleus receptors were tested both on the flexion-extension axis and with a combined adduction-eversion movement. For 38 of the 70 soleus receptors examined (54%), firm adduction-eversion produced a level of activity greater than that caused by 10 degrees of flexion, and for 77% the level of activity was greater than that caused by 5 degrees of flexion. For 168 of the 184 tibialis anterior receptors studied (91%), firm abduction-inversion produced a level of activity greater than that caused by 10 degrees of extension. Thus few receptors were found that responded exclusively to one axis of rotation. One way in which the position of the ankle joint could be specified in the face of multiaxial receptor activity is by examining the receptor discharge from more than one muscle. A suggestion for how the nervous system might do this is given in the discussion.

Afferent Pathways↗
PubMed1984

Actions of substance P on rat spinal dorsal horn neurones.

The membrane actions of substance P (SP) and the effects on the Ca-dependent action potential of dorsal horn neurones have been investigated by means of intracellular recording techniques in the immature rat in vitro spinal cord slice preparation. Bath application of SP (2 X 10(-6) to 1 X 10(-5) M) induced a biphasic membrane response consisting of an initial hyperpolarization followed by a depolarization in about one-third of the cells examined. Initial hyperpolarization was not observed when synaptic activity was blocked by perfusing the slice with a tetrodotoxin-containing or low Ca, high Mg Ringer solution. This result is consistent with a presynaptic action of SP mediated through excitation of inhibitory interneurones. This interpretation was supported by recording of repetitive spontaneous inhibitory post-synaptic potential (i.p.s.p.)-like hyperpolarizing potentials during the initial hyperpolarization. When Co ions were used to block voltage-dependent Ca conductance and possible indirect presynaptic actions, SP induced only a small depolarization of membrane potential. It seems, therefore, that Ca conductance may have contributed to the depolarizing phase of the SP response, either through its mediation of synaptic transmission or through direct effects as a charge carrier for inward current. When tetrodotoxin was used, the SP-induced increase in neuronal input resistance was not modified, although depolarization was slightly diminished. In contrast, in medium containing tetrodotoxin and tetraethylammonium, the SP-depolarizing response was enhanced and accompanied by a small decrease in input resistance and firing of Ca spikes. These results suggest that SP-induced depolarization might be a consequence of a reduction in a voltage-dependent K conductance allowing Na and/or Ca conductances to dominate. SP modified the duration of Ca-dependent action potentials of dorsal horn neurones, the most consistent change being an initial dose-dependent and reversible decrease in the spike duration. The decrease in Ca spike duration was associated with a small reduction in the rate of rise and peak amplitude, and a significant parallel increase in dV/dt of the falling phase of the Ca spike. Our data indicate that the initial decrease in Ca spike duration was not due to the depolarizing action of SP, although shunting of the membrane resistance, either through presynaptic or post-synaptic mechanisms, has not been ruled out. Alternatively, these data are consistent with the possibility that SP shortens the duration of the Ca spike by decreasing a voltage-sensitive inward Ca current and/or augmenting an outward K current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1983

Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium-dependent action potentials.

1. The electrophysiological properties of dorsal horn neurones have been investigated in the immature rat in vitro spinal cord slice preparation. 2. Intracellular recordings from dorsal horn neurones show that direct or orthodromic stimulation generates action potentials followed by a brief after-hyperpolarization. Synaptic potentials were elicited by the activation of primary afferent fibres in the dorsal root. 3. Input resistance for dorsal horn neurones ranged from 48 to 267 M omega, and the membrane time constant was in the range of 4-19 ms. 4. In response to strong depolarizing currents dorsal horn neurones perfused with TTX and TEA frequently exhibit a slow regenerative depolarizing potential followed by a slow after-hyperpolarization. The depolarizing potential probably results from an influx of Ca. It is blocked by low concentration Ca, Co or Mn, and enhanced by high levels of extracellular Ca. 5. There is, in addition, a low-threshold Ca-dependent response which is activated at membrane potentials more negative than -65 mV and has a maximum rate of rise at the polarization level of about -80 mV. 6. The addition of Ba or TEA to the perfusing medium provided support for the Ca-dependence of the low- and high-threshold responses, and the lack of fast inactivation of the high-threshold Ca potential.

Action Potentials↗
PubMed1982

The actions of neuropeptides on dorsal horn neurons in the rat spinal cord slice preparation: an intracellular study.

Responses of dorsal horn neurons to bath application of substance P, somatostatin and enkephalin were studied by intracellular recording in the neonatal spinal cord slice preparation. Substance P depolarized dorsal horn neurons and increased their excitability. The depolarization was most commonly associated with an increase in neuronal input resistance. Somatostatin and enkephalin hyperpolarized dorsal horn neurons and caused reduction or abolition of spontaneous firing. While the hyperpolarization produced by enkephalin was always associated with a fall in neuronal input resistance, in the case of somatostatin the similar effect was less consistently observed.

Animals↗
PubMed1981

Effect of iontophoretically applied 5-hydroxytryptamine on the excitability of single primary afferent C- and A-fibers in the cat spinal cord.

Excitability testing of single sural afferent C- and A-fibers was employed to study possible presynaptic effects of 5-hydroxytryptamine (5-HT) applied iontophoretically at the intraspinal point of lowest threshold for their antidromic activation in anesthetized or decerebrate spinalized cats. Threshold for single fibers recorded in the sural nerve was measured prior to and during iontophoretic application of 5-HT through a micropipette positioned in close proximity to the intraspinal stimulating electrode. 5-HT produced dose-related increases in threshold for antidromic activation in 21 or 30 C-fibers. Six of 9 A delta, and 4 of 7 A beta-fibers were similarly affected.

Afferent Pathways↗
PubMed1981

Norepinephrine reduces excitability of single cutaneous primary afferent C-fibers in the cat spinal cord.

An excitability testing procedure of single afferent C-fibers was used to study possible presynaptic actions of norepinephrine (NE) applied to locally at the intraspinal sites of minimal threshold for their antidromic activation in spinalized cats. NE, applied by iontophoresis and/or pressure microinjection, produced dose-related increases in threshold for antidromic activation in 44 of 65 C-fibers. It was concluded that in addition to previously shown postsynaptic depressant action, NE reduces excitability of intraspinal cutaneous C-fibers.

Afferent Pathways↗
PubMed1981

Cholecystokinin octapeptide excites dorsal horn neurons both in vivo and in vitro.

Cholecystokinin octapeptide (CCK-8) applied microiontophoretically causes a moderate to strong excitation of about half of all tested dorsal horn neurons located in laminae I-VII of both the cat intact spinal cord and the rat in vitro spinal cord slice preparation. In the cat intact spinal cord the excitation is not limited to a single population of neurons but is observed in all categories of units recognized in spinal preparations of cats in this area on the basis of their excitability by different kinds of cutaneous afferent input. In the spinal cord slice preparation the excitatory action of CCK-8 persists even when the spinal cord slices are perfused with a Ca2+-free, Mg2+-high Krebs solution. The latter finding indicates that the action of CCK-8 might be a direct one exerted on the postsynaptic sites of dorsal horn units. These results are consistent with the possibility that CCK-8 acts on postsynaptic sites in the dorsal horn of the spinal cord as a neurotransmitter or modulator.

Animals↗
PubMed1981

A morphological study of cat dorsal spinocerebellar tract neurons after intracellular injection of horseradish peroxidase.

This work represents an attempt to elucidate structural features of electrophysiologically characterized, individual cat dorsal spinocerebellar tract (DSCT) neurons by using intracellular application of horseradish peroxidase (HRP). Intracellular recordings and HRP injections were made in DSCT neurons of the Clarke's column in cat lumbar (L3) spinal cord. The units were identified by antidromic invasion following electrical stimulation of the ipsilateral dorsolateral funiculus at C1. In addition, sensory inputs to the DSCT neurons were determined by natural (adequate) stimuli applied to the hind limb with intact innervation. The morphological analysis is based on data obtained from 19 well-stained electrophysiologically identified neurons located in Clarke's column. Thirteen of these units received excitatory sensory inputs from muscle receptors, two were activated by cutaneous afferents only, and four had a convergent (muscle + cutaneous) input. The DSCT--muscle cells were equivalent to the large Clarke cells (class C of Leowy, '70). Their dendrites were oriented primarily in the rostro--caudal direction (up to 2500 micron) and appeared generally smooth except for some branchlets. In four of these cells, the axon was traced into the lateral funiculus. In light microscopic analysis there was no evidence that axon collaterals arose from these axons during the initial trajectory through the spinal grey matter. The four DSCT--convergent neurons were similar in shape to the DSCT--muscle units although they appeared to have somewhat smaller cell bodies. Of the two DSCT--cutaneous neurons one was found to be of the B type, with the dendritic tree having fewer branches and oriented mainly in the medio--lateral direction. The other cell, however, turned out to be similar in appearance to the C type Clarke neurons.

Afferent Pathways↗
PubMed1981

Neonatal rat spinal cord slice preparation: postsynaptic effects of neuropeptides on dorsal horn neurons.

In the neonatal rat spinal cord slice preparation responses of the dorsal horn interneurons to iontophoretic or bath application of methionine-enkephalin (ME), substance P (SP) and somatostatin (SS) were qualitatively similar to those obtained in intact spinal cord. Thus, SP powerfully excited almost all neurons tested (15/16), while ME and SS depressed neuronal discharges in 13/14 and 4/6 units respectively. In some dorsal horn neurons the iontophoretic application of ME caused a marked depression of the SP-induced excitation. Angiotensin II (AgII) had no effect on dorsal horn units (n = 8). In the slices perfused with a Ca2+-free, Mg2+-high Krebs solution the extracellularly recorded effects of ME, SP and SS were not significantly modified, suggesting that the peptides were acting directly on postsynaptic sites. The results also indicate that the in vitro rat spinal cord slice preparation can be successfully utilized for further studies on the cellular mechanisms of actions of neuropeptides, particularly in relation to synaptic transmission processes in the dorsal horn.

Angiotensin II↗