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T J Ruigrok

Publications and source records attributed to T J Ruigrok.

At least 19 recordsLinked to original sources
PubMed2001

Brain death-related energetic failure of the donor heart becomes apparent only during storage and reperfusion: an ex vivo phosphorus-31 magnetic resonance spectroscopy study on the feline heart.

BACKGROUND AND OBJECTIVE: Recently, we have shown, by using localized in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) of the anterior left ventricular wall, that brain death (BD) is not associated with reduced myocardial energy status. In this study, we applied ex vivo 31P MRS of the entire heart to study the effects of BD on the energy status of the feline donor heart following explantation. METHODS: We used cats (6 BD and 6 controls [C]) in a 26-hour protocol. After 2 hours of preparation, we induced BD by filling an intracranial balloon at t = 0 hour. At t = 6 hours, the hearts were arrested with St. Thomas' Hospital cardioplegic solution, explanted, and stored in the same solution at 4 degrees C in a 4.7 Tesla magnet for 17 hours. Subsequently, the hearts were reperfused in the Langendorff mode at 38 degrees C for 1 hour. The first 5-minute 31P MRS spectrum was obtained 1 hour after crossclamping the aorta; we obtained subsequent spectra every hour during storage and every 5 minutes during reperfusion. At the end, the hearts were dried and weighed. Phosphocreatine (PCr), gamma-adenosine triphosphate (gamma-ATP), inorganic phosphate (Pi), and phosphomonoesters (PME), were expressed per g dry heart weight. The intracellular pH (pH(i)) and the PCr/ATP ratio were calculated. RESULTS: During storage, we identified a significant but similar decrease of pH(i), PCr/ATP ratio, and PCr in both groups. During reperfusion, pH(i) and PCr/ATP ratio recovered similarly in both groups, whereas the recovery of PCr in the BD group was significantly lower (p < 0.05). The Pi and PME increased in both groups during storage but to a lesser extent in the BD group (p < 0.05). This difference disappeared during reperfusion. The gamma-ATP was already significantly lower in the BD group at the onset of storage, and this remained so throughout storage and reperfusion (p < 0.05 vs C). Contractile capacity was lost in all hearts, except for 1 heart in the BD group. CONCLUSION: Brain death-related failure of the energetic integrity of the feline donor heart becomes apparent only when using 31P MRS during ischemic preservation and subsequent reperfusion.

Animals↗
PubMed2001

Postischemic Na(+)-K(+)-ATPase reactivation is delayed in the absence of glycolytic ATP in isolated rat hearts.

Normalization of intracellular sodium (Na) after postischemic reperfusion depends on reactivation of the sarcolemmal Na(+)-K(+)-ATPase. To evaluate the requirement of glycolytic ATP for Na(+)-K(+)-ATPase function during postischemic reperfusion, 5-s time-resolution 23Na NMR was performed in isolated perfused rat hearts. During 20 min of ischemia, Na increased approximately twofold. In glucose-reperfused hearts with or without prior preischemic glycogen depletion, Na decreased immediately upon postischemic reperfusion. In glycogen-depleted pyruvate-reperfused hearts, however, the decrease of Na was delayed by approximately 25 s, and application of the pyruvate dehydrogenase (PDH) activator dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na had almost normalized in all groups and contractile recovery was highest in the DA-treated hearts. In conclusion, some degree of functional coupling of glycolytic ATP and Na(+)-K(+)-ATPase activity exists, but glycolysis is not essential for recovery of Na homeostasis and contractility after prolonged reperfusion. Furthermore, the delayed Na(+)-K(+)-ATPase reactivation observed in pyruvate-reperfused hearts is not due to inhibition of PDH.

Adenosine Triphosphate↗
PubMed2001

No evidence for participation of non-adrenergic non-cholinergic subtances in brain death-related hemodynamic deterioration of the feline potential heart donor.

OBJECTIVE: To onset of brain death (BD) is associated with a hyperdynamic cardiovascular response caused by the acute sympathetic release of catecholamines. This is followed by progressive hemodynamic deterioration which may preclude heart donation for transplantation. The mechanism of the hemodynamic collapse is not fully understood. Changes in plasma concentrations of non-adrenergic non-cholinergic (NANC) substances, neuropeptide-Y (NP-Y, a vasoconstrictor) and the vasodilators calcitonin gene-related peptide (CGRP) and substance P (SP), were studied in relation to BD-related hemodynamic alterations. MATERIALS AND METHODS: Cats (6 BD and 6 controls (C)) were studied for 6 h. Heart rate (HR) and mean arterial pressure (MAP) were monitored. BD was induced at t = O min. At t = -5, 15, 60, 180 and 360 min, 5 ml arterial blood samples were taken. The plasma was collected and analyzed. The correlations between MAP and NANC levels were calculated. RESULTS: In the BD cats a maximal and significant increase in HR and MAP was observed at t = 2 min. HR returned to basal levels at t = 20 min and remained at that level. However, MAP deteriorated progressively to 53 +/- 8 mmHg (p 0.001 vs C) at/ = 360 min. NP-Y had increased from 59.7 +/- 2.5 to 110 +/- 20.2 pmol/l (p 0.05 vs C) at t = 15 min, had returned to basal value at t = 60 min and remained at that level. CGRP levels were lower and SP levels did not change vs C but both showed a trend towards higher levels at t = 360 min. The correlations between MAP and NP-Y, CGRP and SP appeared to be not significant. CONCLUSION: No evidence for participation of NANC substances could be demonstrated in brain death-related hemodynamic deterioration of the feline potential heart donor.

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PubMed2000

Organization of projections from the inferior olive to the cerebellar nuclei in the rat.

The detailed organization of projections from the inferior olive to the cerebellar nuclei of the rat was studied by using anterograde tracing. The presence of a collateral projection to the cerebellar nuclei could be confirmed, and a detailed organization was recognized at the nuclear and subnuclear level. Olivary projections to the different parts of the medial cerebellar nucleus arise from various parts of the caudal half of the medial accessory olivary nucleus. The interstitial cell groups receive olivary afferents from the intermediate part of the medial accessory olive and from the dorsomedial cell column. A mediolateral topography was noted in the projections from the rostral half of the medial accessory olive to the posterior interposed nucleus. Olivary projections to the lateral cerebellar nucleus are derived from the principal olive according to basically inversed rostrocaudal topography. Projections from the dorsomedial group of the principal olive to the dorsolateral hump were found to follow a basically rostrocaudal topography. The anterior interposed nucleus receives olivary afferents from the dorsal accessory olive. Its rostromedial parts are directed to the lateral part of the anterior interposed nucleus and its caudolateral part reach the medial anterior interposed nucleus. No terminal arborizations in the cerebellar nuclei were found to originate from (1) the dorsal fold of the dorsal accessory olive, which resulted in projections to the lateral vestibular nucleus and (2) the dorsal cap of Kooy. It was noted that the olivary projection to the cerebellar nuclei is strictly reciprocal to the nucleo-olivary projection as described by Ruigrok and Voogd (1990). Moreover, it is suggested that the olivonuclear projection adheres to the organization of the climbing fiber projection to the cerebellar cortex and to the corticonuclear projection, thus, establishing and extending the detailed micromodular organization of the connections between inferior olive and cerebellum.

Animals↗
PubMed2000

Topography of cerebellar nuclear projections to the brain stem in the rat.

The organization of the cerebellum is characterized by a number of parallel and parasagittally ordered olivocorticonuclear modules; as such, the cerebellar nuclei basically function as output system of these modules. The present study provides a comprehensive and detailed description of the organization of the connections from the cerebellar nuclei to the brain stem in the rat. Thirteen small injections with the anterograde tracer Phaseolus vulgaris leucoagglutinin or biotinylated dextran amine which were centered on various aspects of the cerebellar nuclear complex are described and are illustrated with serial plots detailing the distribution of labeled varicosities throughout the brain stem. In every case at least 1,000 an up to 36,000 varicosities were plotted. All injections resulted in some or heavy labeling concentrated within specific regions of the contralateral inferior olivary complex and, usually, in some labeling of the contralateral ventrolateral thalamus. However, apart from these two areas it is shown that the cerebellar projections are generally very widespread and may be found throughout the entire brain stem. Below, only a survey of main projection areas will be given. Terminal arborizations originating from the rostral part of the medial cerebellar nucleus are mostly found in the caudal half of the brain stem with emphasis on the vestibular nuclear complex, whereas its caudal part rather connects to midbrain areas. Terminals that originate from the dorsolateral protuberance of the medial cerebellar nucleus are distributed more evenly throughout the brain stem and are mostly confined to reticular areas. The interstitial cell groups, interspersed between the medial and both interposed cerebellar nuclei, provide major projections to the ipsilateral vestibular nuclear complex and contralateral mesodiencephalic regions. However, reticular areas are also targeted over a large rostrocaudal range. The medial part of the posterior interposed nucleus sends most projections to the caudomedial red nucleus, prerubral regions and parvicellular reticular formation, all contralateral to the injection site. Projections that originate from more laterally placed injections are directed, apart from the inferior olivary complex, to the rostral half of the contralateral brain stem, where most labeled varicosities are found in the superior colliculus and zona incerta. The anterior interposed nucleus specifically targets the inferior olive, the red nucleus, the pontine reticulotegmental nucleus, the prectectum and the ventrolateral thalamic nucleus. More laterally placed injections also project to the ipsilateral parvicellular reticular formation and deep layers of the spinal trigeminal complex. The latter areas are more specifically targeted by the dorsolateral hump. In addition, its projections are found in the red nucleus and pretectum but do not seem to reach the ventrolateral thalamus. Projections from the lateral cerebellar nucleus are all characterized by a widespread distribution of terminals. Especially, the caudal aspect of the nucleus sends, apart from projections to the deep mesencephalic nucleus, red nucleus, periaquaductal gray, pretectum, prerubral area, and several thalamic regions, prominent projections to the caudal brain stem which terminate in the inferior olive and gigantocellular reticular formation. Projections from the ventral, parvicellular part of the nucleus are mostly, but not exclusively, directed to the rostral half of the brain stem and mainly terminate in the pararubral area, accessory oculomotor nuclei, pretectal areas, zona incerta, and in the parafascicular and ventrolateral thalamic nuclei. We conclude that the impact of the cerebellar nuclei on the brain stem is widespread; projections from different regions of the same cerebellar nucleus may show important differences in distribution of labeled terminals. On the other hand, injections placed in different cerebellar nuclei may result in a simila

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PubMed2000

Cytosolic Ca2+ concentration during Ca2+ depletion of isolated rat hearts.

Reperfusion of isolated mammalian hearts with a Ca2+-containing solution after a short Ca2+-free period at 37 degrees C results in massive influx of Ca2+ into the cells and irreversible cell damage: the Ca2+ paradox. Information about the free intracellular, cytosolic [Ca2+] ([Ca2+]i) during Ca2+ depletion is essential to assess the possibility of Ca2+ influx through reversed Na+/Ca2+ exchange upon Ca2+ repletion. Furthermore, the increase in end-diastolic pressure often seen during Ca2+-free perfusion of intact hearts may be similar to that seen during ischemia and caused by liberation of Ca2+ from intracellular stores. Therefore, in this study, we measured [Ca2+]i during Ca2+-free perfusion of isolated rat hearts. To this end, the fluorescent indicator Indo-1 was loaded into isolated Langendorff-perfused hearts and Ca2+-transients were recorded. Ca2+-transients disappeared within 1 min of Ca2+ depletion. Systolic [Ca2+]i during control perfusion was 268 +/- 54 nM. Diastolic [Ca2+]i during control perfusion was 114 +/- 34 nM and decreased to 53 +/- 19 nM after 10 min of Ca2+ depletion. Left ventricular end-diastolic pressure (LVEDP) significantly increased from 13 +/- 4 mmHg during control perfusion after Indo-1 AM loading to 31 +/- 5 mmHg after 10 min Ca2+ depletion. Left ventricular developed pressure did not recover during Ca2+ repletion, indicating a full Ca2+ paradox. These results show that LVEDP increased during Ca2+ depletion despite a decrease in [Ca2+]i, and is therefore not comparable to the contracture seen during ischemia. Furthermore, calculation of the driving force for the Na+/Ca2+ exchanger showed that reversed Na+/Ca2+ exchange during Ca2+ repletion is not able to increase [Ca2+]i to cytotoxic levels.

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PubMed1999

Bio-energetic response of the heart to dopamine following brain death-related reduced myocardial workload: a phosphorus-31 magnetic resonance spectroscopy study in the cat.

OBJECTIVE: Long-term exposure of the donor heart to high dosages of dopamine in the treatment of brain death-related hemodynamic deterioration has been shown to reduce myocardial phosphocreatine (PCr) and adenosine triphosphate (ATP) in myocardial biopsy specimens and may preclude heart donation for transplantation. Short-term exposure to the acute catecholamine release during the onset of brain death has shown an unchanged PCr/ATP ratio using in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS). In this study 31P MRS was used to evaluate in vivo myocardial energy metabolism during long-term dopamine treatment. METHODS: Twelve cats were studied in a 4.7 Tesla magnet for 360 minutes. At t = 0 minutes, brain death was induced (n = 6). At 210 minutes, when myocardial workload in the brain-death group was reduced significantly, dopamine was infused (n = 12) at 5 microg/kg/min and its dose was consecutively doubled every 30 minutes and was withheld during the last 30 minutes of the experiment. Phosphorus-31 magnetic resonance spectra were obtained from the left ventricular wall during 5-minute time frames, and PCr/ATP ratios were calculated. The hearts were histologically examined. RESULTS: Although significant changes in myocardial workload were observed after the induction of brain death and during support and withdrawal of dopamine in both groups, the initial PCr/ATP ratio of 2.00+/-0.12 and the contents of PCr and ATP did not vary significantly. Histologically identified sub-endocardial hemorrhage was observed in 3 of 6 of the brain-dead animals and in 1 of 6 of the control animals. CONCLUSIONS: High dosages of dopamine in the treatment of brain death-related reduced myocardial workload do not alter PCr/ATP ratios and the contents of PCr and ATP of the potential donor heart despite histologic damage.

Adenosine Triphosphate↗
PubMed1999

Inferior olivary-induced expression of Fos-like immunoreactivity in the cerebellar nuclei of wild-type and Lurcher mice.

Earlier behavioural studies have shown that the expression of the immediate-early gene c-fos, as visualized by the immunohistochemical detection of Fos, in the inferior olive (IO) correlated closely with expression in related areas of the cerebellar nuclei. It has been speculated that the expression of c-fos within the cerebellar nuclei may be induced by enhanced spiking activity of the immunopositive neurons in the inferior olive. Two potential mechanisms may play a role in this process: a direct induction by way of the collaterals of the olivary climbing fibres to the cerebellar nuclei, or indirectly, by climbing fibre activity-induced depression of mossy fibre-parallel fibre-induced simple spike frequency of the Purkinje cells resulting in a subsequent disinhibition of the related parts of the cerebellar nuclei. In an attempt to distinguish between these possible mechanisms, we analysed Fos immunoreactivity in the olivocerebellar system of wild-type mice and in the mutant mouse Lurcher which lacks Purkinje cells. The tremorgenic agent harmaline, which is known to induce enhanced and rhythmic firing of olivary neurons was given intraperitoneally to anaesthetized mice of both genotypes. Harmaline application coincides with the induction of Fos-immunoreactive neurons in most areas of the IO in both wild-type and Lurcher mice. Both types of mice also showed enhanced expression in the larger neurons of the cerebellar nuclei. However, in the smaller, GABAergic nucleo-olivary neurons, increased c-fos expression was only observed in the wild-type mice. We conclude that: (i) increased olivary activity indeed may result in increased c-Fos expression in related areas of the cerebellar nuclei; (ii) because the indirect mode of induction is not operative in Lurcher mice, the olivary collateral innervation of the cerebellar nuclei is sufficient for c-fos induction in the larger nucleobulbar neurons in Lurcher and potentially also in wild-type mice; however (iii) for the nucleo-olivary cells an intact cerebellar cortical input is necessary to evoke increased expression of c-fos following harmaline application.

Animals↗
PubMed1998

Light microscopic and ultrastructural investigation of the dopaminergic innervation of the ventrolateral outgrowth of the rat inferior olive.

The ventrolateral outgrowth of the inferior olive is involved in the control of compensatory eye movement responses to optokinetic stimuli about the horizontal axis that is perpendicular to the ipsilateral anterior semicircular canal. Combining immunocytochemistry with retrograde tracing of WGA-BSA-gold, we demonstrated in the present study that this olivary subnucleus receives a substantial dopaminergic input, and that the prerubral parafascicular area and its surrounding regions form the sole source of this input. In addition, we investigated the postsynaptic distribution of the dopaminergic terminals in the inferior olive at the ultrastructural level. About a third (32%) of the dopaminergic terminals was found to make synaptic contacts in the olivary neuropil. The majority (81%) of these boutons terminated on cell bodies or extraglomerular dendrites, while the remaining terminals contacted dendritic spines inside glomeruli. In contrast, GABAergic terminals in the inferior olive formed more frequently (66%) synaptic contacts and they terminated more frequently (38%) in glomeruli. Thus, the ventrolateral outgrowth receives a dopaminergic input from the mesodiencephalic junction, and the postsynaptic distribution of this input reveals a characteristic pattern.

Animals↗
PubMed1998

Single Purkinje cell can innervate multiple classes of projection neurons in the cerebellar nuclei of the rat: a light microscopic and ultrastructural triple-tracer study in the rat.

Two different populations of projection neurons are intermingled in the cerebellar nuclei. One group consists of small, gamma-aminobutyric acid-containing (GABAergic) neurons that project to the inferior olive, and the other group consists of larger, non-GABAergic neurons that provide an input to one or more, usually premotor, centers in the brainstem, such as the red nucleus, the thalamus, and the superior colliculus. All cerebellar nuclear neurons are innervated by GABAergic Purkinje cells. In this study, we investigated whether individual Purkinje cells of the C1 zone of the paramedian lobe of the rat innervate both groups of projection neurons in the anterior interposed nucleus. Two different, retrogradely transported tracers, either cholera toxin beta subunit (CTb) or wheat germ agglutinin coupled to horseradish peroxidase (WGA-HRP) and a gold lectin tracer were injected into the red nucleus and the inferior olive, respectively, whereas Purkinje cell axons were anterogradely labeled with biotinylated dextran amine (BDA) injected into the paramedian lobule. Cerebellar nuclear sections studied with the light microscope demonstrated a close relation of varicosities from BDA-labeled Purkinje cell axons with both gold lectin- and CTb-labeled neurons. Branches of individual axons could be traced to both retrogradely labeled cell populations. At the ultrastructural level, synapses of labeled Purkinje cell terminals with profiles of WGA-HRP-labeled projection neurons predominated over contacts with gold lectin-containing neurons. Nine out of 367 investigated BDA-labeled terminals were observed to be presynaptic to a WGA-HRP-labeled profile as well as to a gold lectin-labeled profile. This indicates that nuclear cells that project to the inferior olive as well as those that project to premotor centers are under the influence of the same Purkinje cells. Such an arrangement would suggest an in-phase cortical modulation of the activation patterns of the inhibitory cells that project to the inferior olive and excitatory cells that project to premotor nuclei, which could explain why olivary neurons, especially those of the rostral part of the dorsal accessory olive, appear to be unresponsive to stimuli generated during active movement.

Animals↗
PubMed1998

Manipulation of intracellular sodium by extracellular divalent cations: a 23Na and 31P NMR study on intact rat hearts.

23Na and 31P NMR spectroscopy were used to follow intracellular [Na+] ([Na+]i) and energy metabolism in isolated, perfused rat hearts. During 30 min of Ca(2+)-free perfusion no significant change in [Na+]i could be detected, but during a subsequent 45 min period of ischemia [Na+]i rose significantly as expected, from 8.6 +/- 2.4 to 36.8 +/- 9.4 mM. In contrast, already during 30 min of Ca(2+)- and Mg(2+)-free perfusion [Na+]i rose significantly from 7.3 +/- 3.7 to 71.3 +/- 15.6 mM. During this period, the Na(+)-K+ ATPase was not limited by depletion of high energy phosphates, decrease of intracellular free Mg2+ or accumulation of inorganic phosphate. During the first 8 min of a subsequent period of ischemia, the rate of rise in [Na+]i even increased, suggesting that during the preceding period of Ca(2+)- and Mg(2+)-free perfusion, the Na(+)-K+ ATPase was indeed operative but apparently not coping with the large Na(+)-influx. Using verapamil, we could demonstrate that this large Na(+)-influx occurs through the L-type Ca2+ channels, and that both Mg2+ and verapamil can block this Na(+)-influx. Previously, we have demonstrated that [Na+]i does not play a role in the origin of the calcium paradox. The notion that an increased [Na+]i is a prerequisite for the calcium paradox to occur apparently results from experimental evidence obtained under conditions of low or absent Mg2+.

Adenosine Triphosphate↗
PubMed1998

Both Na+-K+ ATPase and Na +-H+ exchanger are immediately active upon post-ischemic reperfusion in isolated rat hearts.

Limited time resolution has hampered proper evaluation of changes in intracellular Na+ (Na+i) in whole hearts upon post-ischemic reperfusion. In isolated rat hearts perfused at 37 degrees C, we studied the contribution of the Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+i during reperfusion using 23Na NMR and the shift reagent Tm(DOTP)5- with a time resolution of 5 s. To assess activities of the Na +-K+ ATPase and the Na+-H+ exchanger, 250 micro mol/l ouabain and/or 3 micro mol/l EIPA, respectively, was added to the perfusate during the first 5 min of reperfusion, following 20 min of ischemia. When used, ouabain was also present for 2 min prior to ischemia. Na+i increased during ouabain perfusion prior to ischemia (132+/-5 and 133+/-4% of the pre-ischemic control value after 2 min, in ouabain and ouabain+EIPA hearts, respectively; mean+/-s.e.m.; n=6 per group) resulting in higher end-ischemic values in ouabain and ouabain+EIPA hearts (249+/-9 and 267+/-17% of the pre-ischemic control value, respectively) than in control and EIPA hearts (207+/-21 and 199+/-10% of the pre-ischemic control value, respectively). In ouabain, hearts Na+i started to rise directly upon reperfusion and amounted to 117+/-6% of the end-ischemic value after 60 s of reperfusion. In control hearts, however, Na+i dropped immediately and was 87+/-5% of the end-ischemic value after 60 s, indicating that the Na+-K+ ATPase resumed function directly upon reperfusion. The initial steep increase of Na+i upon reperfusion in ouabain hearts, which diminished after approximately 40 s to the rate of increase observed during ischemia, was absent in ouabain + EIPA hearts. This indicates the existence, although masked by Na+-K+ ATPase activity, of a Na+-H + exchange mediated Na+ influx upon reperfusion. If only EIPA was present during reperfusion the initial decrease in Na+i was faster than in control hearts, corroborating this finding.

Amiloride↗
PubMed1998

Na+/Ca2+ exchange during Ca2+ repletion is not a prerequisite for the Ca2+ paradox in isolated rat hearts.

Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. Since previously a Ca2+ paradox without prior increase of total intracellular [Na+] ([Na+]i) has been observed, we investigated whether local accumulation of Na+ close to the inner side of the sarcolemma during Ca2+ depletion plays a role in the Ca2+ paradox by replacing all extracellular Na+ by Li+ 5 min before and during 10 min Ca2+-free perfusion (37°C) in isolated rat hearts (group I). Subsequently, hearts were perfused with a standard, Na+- and Ca2+-containing solution. Verapamil was used to prevent contracture due to the absence of Na+/Ca2+ exchange during Na+-free perfusion in the presence of Ca2+. In group II, the Ca2+-free period was omitted, and in group III normal extracellular [Na+] was used throughout. 23Na-NMR was used to monitor intra- and extracellular Na+ signals. Total creatine kinase release was 2,977±413, 36±24 and 3170±297 IU/g dry weight in groups I, II and III respectively, indicating a full Ca2+ paradox in groups I and III. [Na+]i decreased from 11.3±0.6 mM during control perfusion to 1.2±0.4 mM after 10 min Ca2+ depletion in group I, whereas in group III [Na+]i was 10.9±2.2 mM during control perfusion and did not change significantly after 10 min Ca2+-free perfusion. It is concluded that accumulation of Na+ close to the inner side of the sarcolemma during Ca2+ depletion is not a prerequisite for the Ca2+ paradox.

Animals↗
PubMed1998

Microcircuitry and function of the inferior olive.

The inferior olive, which provides the climbing fibers to Purkinje cells in the cerebellar cortex, has been implicated in various functions, such as learning and timing of movements, and comparing intended with achieved movements. For example, climbing-fiber activity could transmit error signals during eye-blink conditioning or adaptation of the vestibulo-ocular reflex, or it could carry motor command signals beating on the rhythm of the oscillating and synchronous firing of ensembles of olivary neurons, or both. In this review, we approach the controversial issue of olivocerebellar function from the perspective of the unique organization of the microcircuitry of the olivary neuropil. The characteristic glomeruli are formed by a core of long dendritic or axonal spines, each of which is innervated by both an inhibitory terminal derived from the hindbrain and an excitatory terminal derived from either an ascending or descending input. The dendritic spines, which originate from dendrites with varicosities carrying dendritic lamellar bodies, are coupled by gap junctions. By drawing a comparison with a computational model by Segev and Rall,which might be applicable to the typical olivary spine with its unique morphological features and combined excitatory and inhibitory input, we propose that the microcircuitry of the inferior olive is capable of functioning both in motor learning and motor timing, but does not directly compare intended with achieved movements.

Animals↗
PubMed1998

An increase in intracellular [Na+] during Ca2+ depletion is not related to Ca2+ paradox damage in rat hearts.

Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of 23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25 degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2 to 26.9 +/- 5.8 mM (P < 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C, whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine kinase release during normothermic Ca2+ repletion in the 20 degrees C groups was approximately 10% and in the 25 degrees C groups 75% of the release in the normothermia group. Recovery of rate-pressure product was approximately 50% in the 20 degrees C groups versus 0% in the normothermia group. In conclusion, hypothermic Ca2+/Mg(2+)-free perfusion results in a significant increase of [Na+]i, which does not contribute to the extent of the Ca2+ paradox on normothermic Ca2+ repletion.

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