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M Randic

Publications and source records attributed to M Randic.

At least 19 recordsLinked to original sources
PubMed2000

Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn.

The effects of group II and group III metabotropic glutamate receptor agonists on synaptic responses evoked by primary afferent stimulation in the dorsal horn, but mostly substantia gelatinosa, neurons were studied in the spinal cord slice preparation using conventional intracellular recording technique. Bath application of a potent metabotropic glutamate receptor 2- and 3-selective agonist (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine reversibly suppressed monosynaptic and polysynaptic excitatory postsynaptic potentials evoked by A primary afferent fibers stimulation, the effect likely mediated by mGlu3 receptor subtype. This suppressing effect of (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine on primary afferent neurotransmission was dose dependent and reduced by (S)-alpha-ethylglutamate, a group II metabotropic glutamate receptor antagonist. (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl) glycine suppressed excitatory postsynaptic potentials without inducing detectable changes of postsynaptic membrane potential and neuronal input resistance in dorsal horn neurons. The paired-pulse depression at excitatory synapses between primary afferent fibers and dorsal horn neurons was reduced by (2S,1'R,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine application, suggesting a presynaptic site of action. The selective group III metabotropic glutamate receptor agonist (S)-2-amino-4-phosphonobutanoate also depressed A afferent fibers-evoked monosynaptic and polysynaptic excitatory postsynaptic potentials in a dose-dependent and reversible manner. The concentration-dependence of (S)-2-amino-4-phosphonobutanoate-mediated depression was most consistent with activation of mGlu receptor subtypes 4 and 7. However, on the basis of anatomical distribution of mGlu 4 and 7 subtypes, it is also possible that the (S)-2-amino-4-phosphonobatanoate effect is due to interaction with mGlu 7 receptor alone. (RS)-alpha-cyclopropyl-4-phosphonophenylglycine a preferential antagonist at group III metabotropic glutamate receptors, completely reversed the depressant effects of (S)-2-amino-4-phosphonobutanoate on both monosynaptic and polysynaptic responses. (S)-2-amino-4-phosphonobutanoate reduced the paired-pulse depression at excitatory synapses between primary afferent fibers and dorsal horn neurons, but did not alter their postsynaptic membrane potential and input resistance. A clear facilitation of the (S)-2-amino-4-phosphonobutanoate-induced depression of monosynaptic and polysynaptic excitatory postsynaptic potentials in the absence of gamma-aminobutyric acid-subtype A receptor- and glycine-mediated synaptic inhibition was shown. Besides the depressant effect on excitatory synaptic transmission, inhibitory actions of group II and III metabotropic glutamate receptor agonists on the inhibitory postsynaptic potentials evoked by primary afferent stimulation in dorsal horn neurons were observed. These results suggest that group II and group III metabotropic glutamate receptors are expressed at primary afferent synapses in the dorsal horn region, and activation of the receptors suppresses synaptic transmission by an action on the presynaptic site.

Animals↗
PubMed2000

On numerical characterization of cyclicity

We propose characterizing the cyclicity of molecular graphs by considering their D/DD matrix. Each nondiagonal element of D/DD is a quotient of the corresponding elements of the distance matrix D and the detour matrix DD of a graph. In particular, we are using the leading eigenvalue of the D/DD matrix as a descriptor of cyclicity and are investigating for monocyclic graphs Cn how this eigenvalue depends on the number of vertexes n, as n approaches infinity.

Journal Article↗
PubMed2000

Construction of high-quality structure-property-activity regressions: the boiling points of sulfides

Instead of using the standard molecular descriptors (topological indices) for regression analysis, which are numerically fully determined once a molecule is selected, we outline the use of variable molecular descriptors that are modified during the search for the best regression. The approach is illustrated using boiling points of sulfides. We have transformed the connectivity index 1chi into a function of two variables (x, y) which differentiate carbon and sulfur atoms. The optimal values of the variables (x, y) were determined by minimizing the standard error of the regression. With the values x = +0.25 and y = -0.95 for carbon and sulfur, respectively, we have obtained a regression based on a single descriptor and a standard error of 1.8 degrees C. With elimination of two outliers (having a deviation of about 4 degrees C) the standard error is reduced to a remarkable 1.3 degrees C.

Journal Article↗
PubMed2000

Multiple regression analysis with optimal molecular descriptors.

We consider construction of optimal molecular descriptors to be used for multiple regression analysis of several properties of alcohols. The descriptors are obtained by considering shorter paths with variable weight x for carbon-oxygen bond in alcohol. In particular we consider as molecular descriptors paths of length 1, 2 and 3. The multiple regression analysis of the following molecular properties was examined: - log S (S = solubility), CSA (cavity surface area), log P (P = octanol/water partition), and log gamma (gamma = infinite solution activity coefficient). By minimizing the standard error of the regression for each property we found optimal variable weight.

Alcohols↗
PubMed1996

mu-Opioid receptor-mediated reduction of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-activated current in dorsal horn neurons.

Whole-cell voltage-clamp recording was used to examine the effects of mu-opioid receptor agonists DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephalin) and PL017 (Tyr-Pro-N-MePhe-D-Pro-NH2) on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that the peak and steady-state amplitude of the AMPA-induced current were depressed by mu-opioid agonists (1 nM-5 microM) in a dose-dependent manner in about 80% of the tested cells. When experiments were performed using whole-cell perforated patch technique, similar depression of AMPA current was produced by mu-opioids. The mu-opioid receptor selective antagonist CTAP (100 nM) prevented or reduced the depressant effects of DAGO and PL017. Intracellular dialysis with guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S, 0.2 mM) significantly diminished the PL017-induced depression of AMPA responses. In addition, when the cells were dialyzed with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S, 0.1 mM) the amplitude and duration of the PL017-induced depression was significantly enhanced. Besides depressing the AMPA responses of DH cells, co-application of PL017 and kainic acid (KA) decreased the magnitude of the KA-induced current in 60% of the tested cells. These results indicate that in acutely isolated rat DH neurons, the activation of mu-opioid receptor inhibits AMPA-activated current through activation of a G-protein. This action may contribute to the regulation of the strength of the primary afferent neurotransmission including nociception.

Amino Acid Sequence↗
PubMed1993

Interactions between excitatory amino acids and tachykinins in the rat spinal dorsal horn.

Whole-cell patch-clamp technique of freshly isolated rat spinal dorsal horn (DH) neurons, intracellular recording from DH neurons in a slice preparation, and high performance liquid chromatography with fluorimetric detection of release of endogenous glutamate and aspartate from spinal cord slice following activation of primary afferent fibers were employed to investigate interactions between excitatory amino acids (EAA) and tachykinins [substance P (SP) and neurokinin A (NKA)]. Potentiation of N-methyl-D-aspartate (NMDA)-, quisqualate (QA)- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, but not kainate-induced currents by SP and NKA was found. Spantide II, a claimed novel nonselective tachykinin antagonist, effectively blocked the SP (2 nM)-induced potentiation of the responses of DH neurons to NMDA. In the presence of glycine (0.1 microM), the SP-evoked increase of the NMDA-induced current was prevented. However, 7-chlorokynurenic acid (2 microM), a competitive antagonist at the glycine allosteric site of the NMDA receptor, led to the reestablishment of the SP effect. Brief high frequency electrical stimulation of primary afferent fibers produced a long-lasting potentiation of presumed monosynaptic and polysynaptic excitatory postsynaptic potentials and sustained enhanced release of endogenous glutamate (218.3 +/- 66.1%) and aspartate (286.3 +/- 58.0%). Possible functional implications of the observed phenomena are discussed in relation to transmission and integration of sensory information, including pain.

Afferent Pathways↗
PubMed1993

Tachykinins potentiate N-methyl-D-aspartate responses in acutely isolated neurons from the dorsal horn.

Substance P and neurokinin A both potentiated N-methyl-D-aspartate (NMDA)-induced currents recorded in acutely isolated neurons from the dorsal horn of the rat. To elucidate the mechanism underlying this phenomenon, we measured the effects of tachykinins and glutamate receptor agonists on [Ca2+]i in these cells. Substance P, but not neurokinin A, increased [Ca2+]i in a subpopulation of neurons. The increase in [Ca2+]i was found to be due to Ca2+ influx through voltage-sensitive Ca2+ channels. Substance P and neurokinin A also potentiated the increase in [Ca2+]i produced by NMDA, but not by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, or 50 mM K+. Phorbol esters enhanced the effects of NMDA and staurosporine inhibited the potentiation of NMDA effects by tachykinins. It is concluded that activation of protein kinase C may mediate the enhancement of NMDA effects by tachykinins in these cells. However, the effects of tachykinins on [Ca2+]i can be dissociated from their effects on NMDA receptors.

Animals↗
PubMed1992

Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid.

In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat the effects of 25-100 microM of (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD), 1S,3R-ACPD and 1R,3S-ACPD, a metabotropic glutamate receptor (mGluR) agonist, on inward currents induced by glutamate (Glu), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate were studied under whole-cell voltage-clamp conditions. When the cells were clamped to -60 mV, the racemic mixture and both stereo isomers of trans-ACPD increase the responses elicited by Glu, AMPA, and NMDA, but little those of kainate. In addition, quisqualate (10-50 microM), in the presence of CNQX (5-20 microM) or NBQX (5 microM), potentiated NMDA-induced currents. The enhancing effect lasted 10-75 min, depending upon both dose and length of application. In a smaller proportion of dorsal horn neurons, the enhancing effect was preceded by a transient depression of the responses to Glu, AMPA, and NMDA. 2-Amino-3-phosphonopropionic acid (L-AP3), a putative antagonist of mGluR exerted little effect on responses to AMPA itself, but reduced or prevented the enhancing effect of 1S,3R-ACPD. It is concluded that activation of a metabotropic glutamate receptor by trans-ACPD, and its two enantiomers, may mediate the enhancement of AMPA and NMDA responses in acutely isolated rat spinal dorsal horn neurons. These results are consistent with the possibility that the activation of metabotropic glutamate receptor may contribute to the regulation of the strength of excitatory amino-mediated primary afferent neurotransmission, including nociception.

Animals↗
PubMed1992

Modulation of excitatory amino acid responses in rat dorsal horn neurons by tachykinins.

1. In freshly isolated spinal dorsal horn (DH) neurons (laminae I-III) of the young rat, the effects of tachykinins (substance P, neurokinin A) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp conditions. 2. When the cells were clamped to a holding potential of -60 mV, a simultaneous application of N-methyl-D-aspartate (NMDA) (10(-4) M) and substance P (SP) (2 x 10(-9)-10(-7) M) for 10 s reversibly enhanced (by 129.6 +/- 8.2%, mean +/- SE) the peak amplitude of the initial transient component of the NMDA-induced current in approximately 60% of the examined cells and reduced it (to 83.3 +/- 2.7%) in 27% of the cells. In addition, SP produced an increase (by 133.6 +/- 11.7%) or a small decrease (to 85.9 +/- 1.4%) in the steady-state component of the NMDA response. In difference to SP, a simultaneous application of NMDA (10(-4) M) and neurokinin A (NKA) (10(-10)-10(-7) M) reversibly suppressed (to 86.8 +/- 2.1%) the peak amplitude of the NMDA-induced current in 75% of the examined cells. 3. The NMDA-induced currents were modulated by tachykinins not only during the coadministration but up to 20 min after the removal of the peptide. SP potentiated the initial peak NMDA current by 147.9 +/- 8.1% in 78% of examined cells and decreased it (76.3 +/- 5.7%) in 11% of cells. The potentiating effect was concentration-dependent (range: 10(-11)-10(-8) M) and reversible, but it was reduced with repeated applications. In addition, SP increased (by 125.4 +/- 3.6%) or reduced (to 86.0 +/- 1.8%) the steady-state component of the NMDA response. 4. When the single DH neurons were exposed to SP or NKA for 30 s-7 min before the testing of the NMDA responses, tachykinins had two distinct effects on the peak amplitude of the transient component of the NMDA-induced current, consisting of an initial depression (SP: to 64.8 +/- 2.1%; NKA: to 76.3 +/- 4.4%) followed by a potentiation (SP: by 146.6 +/- 6.8%; NKA: by 178.4 +/- 35.2%). The enhancing effect in some cells lasted less than or equal to 1 h. 5. A claimed novel nonselective tachykinin antagonist, spantide II (10(-8) M) coadministered with NMDA (10(-4) M), slightly depressed the peak component of NMDA-induced current. In addition, it effectively blocked the SP-induced potentiation of the responses of DH neurons to NMDA.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1990

Serotonin suppresses N-methyl-D-aspartate responses in acutely isolated spinal dorsal horn neurons of the rat.

In acutely isolated spinal dorsal horn neurons of the rat, effects of serotonin (5-hydroxytryptamine, 5-HT) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp condition. 5-HT suppressed the response to N-methyl-D-aspartate (NMDA), but not the response to kainate or quisqualate. This inhibitory effect of 5-HT on NMDA response was present at 5-HT concentrations as low as 10(-15) M. Although the 5-HT effect exhibited similar pharmacology to the 5-HT1A-type receptors, it was not mimicked by increasing intracellular concentration of adenosine 3',5'-cyclic monophosphate that is the common second messenger for 5-HT1A receptors in the mammalian central nervous system. Glycine strongly antagonized this inhibitory effect of 5-HT, and 5-HT reduced opening of NMDA-gated single channels recorded from the outside-out membrane patch. These lines of evidence are consistent with a possibility that 5-HT might directly modulate the NMDA receptor-ion channel complex, either by interacting with the regulatory site(s) or by acting on a distinct site.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

The effects of substance P and calcitonin gene-related peptide on the efflux of endogenous glutamate and aspartate from the rat spinal dorsal horn in vitro.

Bath applied SP (2 x 10(-7) to 5 x 10(-7) M) produced a significant increase in the concentration of glutamate in the spinal slice perfusate, whereas the efflux of aspartate increased only with a higher concentration of SP (5 x 10(-6) M). The enhancement of the basal efflux of glutamate persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, a SP analogue claimed to be an antagonist of synthetic SP. Calcitonin gene-related peptide (CGRP 10(-7) M) produced a significant increase in the concentrations of glutamate and aspartate in the perfusate. Neonatal capsaicin treatment prevented the SP-induced increase in the release of glutamate. In contrast, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that SP and CGRP are capable of modulating the basal efflux of endogenous aspartate and glutamate and this modulation may represent one of the mechanisms by which these peptides contribute to primary afferent synaptic transmission.

Animals↗
PubMed1990

Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurons.

1. Calcium currents in immature rat spinal dorsal horn neurons in transverse slices were studied with the single-electrode voltage-clamp technique. Using experimental conditions that minimized voltage-dependent Na+ and K+ currents, we distinguished low- and high-voltage-activated calcium currents on the basis of their voltage dependence and sensitivity to the Ca2(+)-channel agonist and antagonist drugs. 2. The low-voltage-activated transient calcium current is evoked with weak depolarizing voltage commands. It begins to activate at potentials positive to -70 mV and increases in amplitude and rate of decay with depolarization, the peak values being reached between -40 and -30 mV. The current is fully activated at a holding potential of about -110 mV. Steady-state inactivation is complete at potentials in the range of -60 to -50 mV. 3. The transient component of the high-threshold calcium current appears at membrane potentials close to -40 mV and slowly decays within several hundreds of milliseconds. The amplitude of the current increases with more negative holding potentials (-100 to -40 mV). 4. The sustained component of the high-threshold calcium current seems to activate at potentials positive to -40 mV and exhibits little inactivation during 0.3- to 0.5-s depolarizing commands. This component is better isolated at more depolarized holding potentials (between -40 and -30 mV) that inactivate the transient components of the low- and high-threshold calcium currents. 5. A rundown of calcium currents was seen in dorsal horn cells. The time stability of the transient and sustained components of the high-threshold calcium current was lower than that of the low-threshold transient current. The latter current seemed to be insensitive up to 1 h. 6. (-)-Bay K 8644 (1-10 microM), a dihydropyridine agonist, enhanced the high-threshold calcium current, in particular the sustained component, but not the transient low-threshold calcium current. The dihydropyridine antagonist nifedipine (5-50 microM) selectively reduced the sustained component of the high-threshold calcium current while having little or no effect on the transient components of the low- and high-threshold calcium currents. 7. Cadmium ions (60-100 microM) and cobalt ions (2 mM) markedly reduced both components of the high-threshold calcium current, and Cd2+ only slightly decreased the low-threshold transient current. However, all three components are indiscriminately blocked by higher concentrations of Cd2+ and Co2+.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice.

The effects of dorsal root stimulation and of substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) on the basal release of 9 endogenous amino acids, including glutamate (Glu) and aspartate (Asp), have been investigated using the rat spinal cord slice-dorsal root ganglion preparation and high-performance liquid chromatography with fluorimetric detection. High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)-dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr). Low concentrations of SP (2 x 10(-7) M) caused a selective increase in the rate of basal release of Glu, whereas higher concentrations (1-5 x 10(-6) M) produced, in addition, an increase in the basal release of Asp. The SP-induced increase of Glu persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, an SP analog claimed to be an antagonist of the synthetic SP. NKA (5 x 10(-7) - 10(-6) M), a related tachykinin coexpressed with SP in primary sensory neurons, enhanced the basal release of Gly. CGRP (10(-7) M) caused a significant, largely Ca2(+)-independent increase in the basal release of Glu and Asp and a decrease in asparagine. SP and CGRP potentiated the electrically evoked release of Glu and Asp. Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu. However, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission. The enhancement of the basal and the dorsal root stimulation-evoked release of Glu and Asp by tachykinins and CGRP may have important physiological implications for strengthening the synaptic connections in the spinal dorsal horn.

Amino Acids↗
PubMed1989

Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons.

The responses to excitatory and inhibitory amino acids and peptides were investigated in isolated rat spinal dorsal horn neurons (laminae I-V) of young rats using the whole-cell voltage-clamp technique. The treatment of spinal slices with low concentrations of enzymes and mechanical dissociation yielded isolated neurons that were sensitive to excitatory amino acids (glutamate, kainate, quisqualate and N-methyl-D-aspartate (NMDA), inhibitory amino acids (gamma-aminobutyric acid (GABA), glycine) and peptides (substance P, calcitonin gene-related peptide (CGRP). The responses of dorsal horn neurons to NMDA were potentiated by glycine and CGRP, whereas GABAA responses were enhanced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Our observations indicate that there is reasonable agreement between many of the responses of isolated neurons and those studied in in vivo and in vitro slice and culture preparations.

Amino Acids↗
PubMed1989

Multiple effects of phorbol esters in the rat spinal dorsal horn.

Spinal cord slice preparation and intracellular recording techniques were used to examine the effects of phorbol esters on the sodium- and calcium-dependent action potentials, the excitatory synaptic transmission, the basal (resting) and the dorsal root stimulation-evoked release of 9 endogenous amino acids, including glutamate and aspartate, and the responsiveness of the rat dorsal horn neurons to excitatory amino acids (glutamic, kainic, quisqualic, and N-methyl-D-aspartic). 4-beta-Phorbol-12, 13-dibutyrate and 4-beta-phorbol-12, 13-diacetate produced minor alterations in membrane potential and resistance, but they broadened the sodium-dependent action potential and reduced the duration of the calcium-dependent action potential. In addition, phorbol esters caused a marked and long-lasting increase in the amplitude and the duration of excitatory postsynaptic potentials (EPSPs) evoked in dorsal horn neurons by orthodromic stimulation of a lumbar dorsal root. Phorbol esters produced a brief increase in the basal and electrically evoked release of endogenous excitatory (glutamic, aspartic) and inhibitory amino acids (glycine, GABA). In addition, the rates of release of alanine, serine, and threonine were also elevated. In the presence of TTX, phorbol esters selectively enhanced, in a reversible manner, the depolarizing responses of dorsal horn neurons to N-methyl-D-aspartic acid and L-glutamate but not the responses to kainic or quisqualic acids. The potentiation of the NMDA response was blocked by APV, a specific NMDA receptor antagonist. Thus, phorbol esters appear to enhance excitatory synaptic transmission in the rat spinal dorsal horn slice preparation by acting both at pre- and postsynaptic sites. Phorbol esters could potentiate excitatory synaptic transmission by acting predominantly at a postsynaptic site (NMDA receptor), since the duration of the increased responsiveness of dorsal horn neurons to glutamate and NMDA correlates better with the enhancement of EPSPs than with the increased release of the stimulation-evoked glutamate and aspartate. The increased release of endogenous amino acids is consistent with a presynaptic (terminal) site of action, but it could also be explained by enhanced interneuronal activity. Although our results suggest that in the rat spinal dorsal horn protein kinase C may have a role in controlling the release of putative excitatory and inhibitory neurotransmitters and may also be involved in the regulation of postsynaptic NMDA receptors, the identity of endogenous substance(s) participating in these effects is presently unknown.

Action Potentials↗
PubMed1988

Calcitonin gene-related peptide enhances calcium current of rat dorsal root ganglion neurons and spinal excitatory synaptic transmission.

The actions of calcitonin gene-related peptide (CGRP) were examined on Ca2+-dependent action potentials and voltage-dependent Ca2+ currents in rat dorsal root ganglion (DRG) neurons in vitro. In addition, we tested the effect of CGRP on excitatory synaptic transmission in the rat spinal dorsal horn. CGRP produced a reversible increase in the amplitude and the duration of the Ca2+ spike of DRG neurons and directly increased the voltage-dependent Ca2+ current by enhancing both the transient and the sustained components of the current. The increase in the Ca2+ current is likely to be responsible for the increase in the Ca2+ spike and facilitation of excitatory synaptic transmission.

Action Potentials↗
PubMed1988

Actions of calcitonin gene-related peptide on rat spinal dorsal horn neurons.

The membrane actions of calcitonin gene-related peptide (CGRP) and the effect on the Ca-dependent action potential of dorsal horn neurons have been investigated by means of an intracellular recording technique in the immature rat in vitro spinal cord slice-dorsal root ganglion preparation. Bath application of CGRP (10(-8)-10(-6) M for 1-10 min) produced a slow reversible depolarization in about one-third of the cells examined. Biphasic membrane response consisting of an initial hyperpolarization followed by a late prolonged depolarization was seen in a smaller proportion of tested cells. Both membrane responses were present, and even enhanced, when synaptic transmission and Na spikes were blocked by perfusing the slice with a TTX-containing Krebs solution. The CGRP-induced membrane changes were also present in media containing TTX and TEA. The CGRP-evoked depolarization was associated with an increase in the input resistance, and enhanced excitability in a majority of neurons tested. In addition, CGRP modified the duration of Ca-dependent action potentials of dorsal horn neurons, the most consistent change being a prolonged increase in the spike duration. Our results are consistent with a neurotransmitter or neuromodulator role for CGRP in the rat spinal dorsal horn.

Action Potentials↗