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V F Rafuse

Publications and source records attributed to V F Rafuse.

16 recordsLinked to original sources
PubMed2005

Neuroprotective properties of cultured neural progenitor cells are associated with the production of sonic hedgehog.

Numerous studies have shown that abnormal motor behavior improves when neural progenitor cells (NPCs) are transplanted into animal models of neurodegeneration. The mechanisms responsible for this improvement are not fully understood. Indirect anatomical evidence suggests that attention of abnormal motor behavior is attributed, at least in part, to the secretion of trophic factors from the transplanted NPCs. However, there is little direct evidence supporting this hypothesis. Here we show that NPCs isolated from the subventricular zone (SVZ) of neonatal mice are highly teratogenic when transplanted into the neural tube of developing chick embryos and are neuroprotective for fetal dopaminergic neurons in culture because they release sonic hedgehog (Shh). In addition, the neuroprotective properties of NPCs can be exploited to promote better long-term survival of transplanted fetal neurons in an animal model of Parkinson's disease. Thus, cultured NPCs isolated from the SVZ can secrete at least one potent mitogen (Shh) that dramatically affects the fate of neighboring cells. This trait may account for some of the improvement in motor behavior often reported in animal models of neurodegeneration after transplantation of cultured NPCs that were isolated from the SVZ.

Animals↗
PubMed2001

Size of myelinated nerve fibres is not increased by expansion of the peripheral field in cats.

This study tests the hypothesis that target size regulates the size of myelinated sensory and motor fibres in peripheral nerves. Cat medial gastrocnemius (MG) muscles were partially denervated and the size of the remaining nerve fibres that sprouted was examined 6.4 +/- 0.9 months later to determine whether nerve fibre size increased with target size. Electrophysiological and morphometric analyses were used to quantify myelinated nerve fibre size. Charge measurements from dorsal and ventral roots were used to electrophysiologically quantify the relative number of cut nerve fibres and the average size of the remaining intact sensory and motor nerve fibres. Medial gastrocnemius muscle and motor unit forces provided indirect measurements of the increase in target size. Conduction velocities and amplitude of unitary action potentials of motor nerve fibres innervating single motor units were also measured after partial denervation. Electrophysiological measurements of nerve fibre size and morphometric measurements of outer fibre perimeters and fibre areas concurred and demonstrated that myelinated nerve fibres supplying partially denervated MG muscles did not increase in size in parallel with the increase in the target size. Thus, unlike non-myelinated nerve fibres, the size of myelinated nerve fibres does not increase as target size increases. Retrograde control of size in non-myelinated but not in myelinated nerve fibres demonstrates differences in plasticity of neurons in the somatic and autonomic nervous systems.

Action Potentials↗
PubMed2000

Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice.

The role of neural cell adhesion molecule (NCAM) in the development and maturation of the neuromuscular junction (NMJ) was explored by characterizing structurally and functionally NMJs from postnatal day 11 (P11) to P30 +/+, +/-, and -/- NCAM null mutant mice. Differences in NCAM levels resulted in alterations in the size and shape of NMJs, with -/- NMJs being smaller. Additionally both the withdrawal of polyneuronal innervation and the selective accumulation of synaptic vesicle protein in the presynaptic terminal were delayed. These observations suggest that the bidirectional signaling responsible for these events is impaired at -/- NMJs. Functionally, miniature end plate potential size, end plate potential size, and quantal content did not differ from that of wild type under either normal or low release conditions. However at normal release conditions, -/- NMJs, unlike +/+ NMJs, lacked paired-pulse facilitation. The most striking abnormality was the inability of NCAM null junctions to maintain transmitter output with repetitive stimuli. Combined electrophysiological and FM1-43-labeling studies suggest that NCAM null junctions are unable either to dock or to mobilize a sufficient number of vesicles at high but physiological rates of transmitter release. Taken together our observations show that many aspects of transmission are normal and, thus, that many presynaptic and postsynaptic molecules have assembled properly in the absence of NCAM. However, the fact that NCAM was required for specific aspects of transmission, including paired-pulse facilitation and reliable transmission with repetitive stimuli, suggests that NCAM either is directly involved in these processes or is required for the proper organization and/or function of other molecules underlying these processes.

Animals↗
PubMed2000

The pattern of avian intramuscular nerve branching is determined by the innervating motoneuron and its level of polysialic acid.

Most skeletal muscles are composed of a heterogeneous population of fast and slow muscle fibers that are selectively innervated during development by fast and slow motoneurons, respectively. It is well recognized that, in both birds and mammals, fast and slow motoneurons have substantially different intramuscular branching patterns, a difference critical for proper motor function. However, the cellular mechanisms regulating these differences in motoneuron branching are unknown. In a previous study, we showed that the fast and slow pattern of intramuscular branching, in a chick muscle containing distinct fast and slow muscle regions, was remarkably similar to normal when formed by foreign motoneurons. Whether this was attributable to some property of the innervating "fast" or "slow" motoneurons or to some property of the developing fast-slow muscle fibers was not determined. To distinguish between these two possibilities, we performed chick-quail hindlimb chimeras to force slow chick plantaris motoneurons to innervate a fast quail plantaris muscle. The pattern of intramuscular nerve branching in the fast plantaris of these chimeras closely resembled the slow branching pattern normally observed in chick slow plantaris muscles. Enzymatic removal of polysialic acid (PSA) from nerve and muscle during normal quail plantaris development dramatically changed the normal fast pattern to more closely resemble a slow pattern. In contrast, removal of PSA from chick plantaris motoneurons and muscle fibers had little effect on the pattern of nerve branching. Together, these results indicate that the pattern of intramuscular nerve branching is determined by the level of PSA on the innervating motoneurons.

Animals↗
PubMed1998

Incomplete rematching of nerve and muscle properties in motor units after extensive nerve injuries in cat hindlimb muscle.

1. Motor units were characterized in partially denervated or completely denervated and reinnervated cat medial gastrocnemius (MG) muscles where the number of innervating motor axons was severely reduced to determine (1) to what extent the nerve and muscle properties are rematched in enlarged motor units, (2) whether the normal size relationships between axon size, unit tetanic force and contractile speed are re-established, and (3) whether the type of nerve injury and/or repair affects the re-establishment of nerve and muscle properties. 2. Single MG units were sampled in (1) partially denervated muscles and in reinnervated muscles after either (2) crushing or (3) transecting the nerve and suturing its proximal end to either the distal nerve stump (N-N), or (4) directly to the muscle fascia (N-M). 3. The majority (75-88 %) of motor units in all muscles were classified as S (slow), FR (fast fatigue resistant), FI (fast fatigue intermediate) and FF (fast fatigable). However, there was an increased number of FI and unclassifiable motor units compared to normal. These results suggest that motor unit properties are not entirely regulated by the reinnervating motoneurone. 4. Despite more overlap in the range of unit force between different motor unit types the tetanic force of each type increased in all muscles when reinnervated by few (< 50 %) motor axons. This increase in unit force was due to an expansion in motor unit innervation ratio. 5. The normal relationships between axon size, unit tetanic force, and contractile speed were re-established in all muscles except when reinnervated by < 50 % of their normal complement of motor units after N-M suture. This lack of correlation was due to the reduced fast glycolytic (FG) fibre size and the proportionately greater increase in force of the S units. 6. After reinnervation the ranges in fibre cross-sectional area within single FF units were very similar to those found within the entire FG fibre population. 7. These results show that when few axons make functional connections in partially denervated or reinnervated muscles the normal relationships between axon size and motor unit contractile properties are re-established provided the nerves regenerate within the distal nerve sheath. This rematching of motoneurone size and motor unit contractile properties occurs primarily because the size of the motor axon governs the number of muscle fibres it supplies.

Animals↗
PubMed1998

Selective fasciculation and divergent pathfinding decisions of embryonic chick motor axons projecting to fast and slow muscle regions.

Proper motor function requires the precise matching of motoneuron and muscle fiber properties. The lack of distinguishing markers for early motoneurons has made it difficult to determine whether this matching is established by selective innervation during development or later via motoneuron-muscle fiber interactions. To examine whether chick motoneurons selectively innervate regions of their target containing either fast or slow muscle fibers, we backlabeled neurons from each of these regions with lipophilic dyes. We found that motor axons projecting to fast and slow muscle regions sorted into separate but adjacent fascicles proximally in the limb, long before they reached the muscle. More distally, these fascicles made divergent pathfinding decisions to course directly to the appropriate muscle fiber region. In contrast, axons projecting to different areas of an all-fast muscle did not fasciculate separately and became more intermingled as they coursed through the limb. Selective fasciculation of fast- and slow-projecting motoneurons was similar both before and after motoneuron cell death, suggesting that motoneurons specifically recognized and fasciculated with axons growing to muscle regions containing the appropriate muscle fiber type. Taken together, these results strongly support the hypothesis that "fast" and "slow" motoneurons are molecularly distinct before target innervation and that they use these differences to selectively fasciculate, pathfind to, and branch within the correct muscle fiber region from the outset of neuromuscular development.

Animals↗
PubMed1997

Innervation ratio and motor unit force in large muscles: a study of chronically stimulated cat medial gastrocnemius.

1. The present study uses chronic low frequency stimulation of cat medial gastrocnemius (MG) muscle to investigate the relative contribution of innervation ratio to the wide range of motor unit force in large mammalian muscles by reducing the normal variation in muscle fibre cross-sectional area and specific force. 2. Isometric force recordings from isolated and physiologically characterized motor units were made 42-240 days after stimulation. Innervation ratio, fibre area and fibre type (I, II A, II B) were determined in one glycogen-depleted motor unit per muscle. 3. After 42 days of stimulation, all motor units were non-fatigable and were classified as either slow (S) or fast-fatigue resistant (FR). Despite the absence of fast-fatigable (FF) motor units, all three muscle fibre types were present, as identified according to their myofibrillar ATPase reactivity. After 143 days, all motor units and muscle fibres were classified as type S and type I, respectively. 4. A rapid decline in muscle and motor unit force to 30% of normal values after 42 days of chronic stimulation was accounted for by a reduction in muscle fibre area. Fibre areas did not change further with longer periods of stimulation but type II fibres were converted to type I. All stimulated muscle fibres were the size of normal type I fibres; the size of the fibres within single motor units covered the full range of the muscle fibre population. 5. In long-term stimulated muscles (> 100 days) when all muscle fibres were type I and all motor units type S, only differences in innervation ratio could account for the remaining range in motor unit force. Estimates of this range from the minimum and maximum values recorded and from values of tetanic force between the 5th and 95th percentiles indicate that the range in innervation ratio in the MG muscles is at least 15-fold and may be as large as 38-fold. Enumerations of glycogen-depleted muscle fibres from single motor units were consistent with this explanation. 6. The findings provide evidence that there is a wide range of innervation ratios in large muscles, which can account for the large range in motor unit forces in the muscles. Since motor unit force and innervation ratio vary with motoneurone size, these studies provide further support that the size of the peripheral field of innervation of motoneurones is related to their size.

Animals↗
PubMed1997

Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. I. Muscle and motor unit properties.

This study of cat medial gastrocnemius (MG) muscle and motor unit (MU) properties tests the hypothesis that the normal ranges of MU contractile force, endurance, and speed are directly associated with the amount of neuromuscular activity normally experienced by each MU. We synchronously activated all MUs in the MG muscle with the same activity (20 Hz in a 50% duty cycle) and asked whether conversion of whole muscle contractile properties is associated with loss of the normal heterogeneity in MU properties. Chronically implanted cuff electrodes on the nerve to MG muscle were used for 24-h/day stimulation and for monitoring progressive changes in contractile force, endurance, and speed by periodic recording of maximal isometric twitch and tetanic contractions under halothane anesthesia. Chronic low-frequency stimulation slowed muscle contractions and made them weaker, and increased muscle endurance. The most rapid and least variable response to stimulation was a decline in force output of the muscle and constituent MUs. Fatigue resistance increased more slowly, whereas the increase in time to peak force varied most widely between animals and occurred with a longer time course than either force or endurance. Changes in contractile force, endurance, and speed of the whole MG muscle accurately reflected changes in the properties of the constituent MUs both in extent and time course. Normally there is a 100-fold range in tetanic force and a 10-fold range in fatigue indexes and twitch time to peak force. After chronic stimulation, the range in these properties was significantly reduced and, even in MU samples from single animals, the range was shown to correspond with the slow (type S) MUs of the normal MG. In no case was the range reduced to less than the type S range. The same results were obtained when the same chronic stimulation pattern of 20 Hz/50% duty cycle was imposed on paralyzed muscles after hemisection and unilateral deafferentation. The findings that the properties of MUs still varied within the normal range of type S MUs and were still heterogeneous despite a decline in the variance in any one property indicate that the neuromuscular activity can account only in part for the wide range of muscle properties. It is concluded that the normal range of properties within MU types reflects an intrinsic regulation of properties in the multinucleated muscle fibers.

Afferent Pathways↗
PubMed1996

Selective innervation of fast and slow muscle regions during early chick neuromuscular development.

The electrical properties of adult motoneurons are well matched to the contractile properties of the fast or slow muscle fibers that they innervate. How this precise matching occurs developmentally is not known. To investigate whether motoneurons exhibit selectivity in innervating discrete muscle regions, containing either fast or slow muscle fibers during early neuromuscular development, we caused embryonic chick hindlimb muscles to become innervated by segmentally inappropriate motoneurons. We used the in vitro spinal cord-hindlimb preparation to identify electrophysiologically the pools of foreign motoneurons innervating the posterior iliotibialis (pITIB), an all-fast muscle, and the iliofibularis (IFIB), a partitioned muscle containing discrete fast and slow regions. The results showed that the pITIB and the fast region of the IFIB were exclusively innervated by motoneurons that normally supply fast muscles. In contrast, the slow region of the IFIB was always innervated by motoneuron pools that normally supply slow muscles. Some experimental IFIB muscles lacked a fast region and were innervated solely by "slow" motoneurons. In addition, the intramuscular nerve branching patterns were always appropriate to the fast-slow nature of the muscle (region) innervated. The selective innervation was found early in the motoneuron death period, and we found no evidence that motoneurons grew into appropriate muscle regions, but failed to form functional contacts. Together, these results support the hypothesis that different classes of motoneurons exhibit molecular differences that allow them to project selectively to, and innervate, muscle fibers of the appropriate type during early neuromuscular development.

Animals↗
PubMed1996

Contractile activity regulates isoform expression and polysialylation of NCAM in cultured myotubes: involvement of Ca2+ and protein kinase C.

Muscle development involves a series of complex cell-cell interactions that are mediated, at least in part, by several different cell adhesion molecules. Previous work from this lab showed that the different isoforms of NCAM and its level of polysialylation are developmentally regulated during chick myogenesis in vivo and that this regulation is important for normal muscle development. Using developing chick secondary myotubes grown in culture, we show here that both the polysialylation of NCAM and the developmental switch in isoform expression are regulated by activity and that Ca2+ entry through voltage-gated channels and the subsequent activation of protein kinase C are required for the developmental changes in NCAM isoform synthesis. Specifically, PSA expression was shown to be developmentally regulated with high expression being temporally correlated with the onset of spontaneous contractile activity. Furthermore, blocking contractile activity caused a decrease in PSA expression, while increasing activity with electrical stimulation resulted in its up-regulation. Immunoblot and metabolic labeling studies indicated that dividing myoblasts synthesize primarily 145-kD NCAM, newly formed, spontaneously contracting myotubes synthesize 130-, 145-, and 155-kD NCAM isoforms, while older, more mature myotubes primarily synthesize the glycosylphosphatidylinositol-anchored 130-kD isoform which, in contrast to the other three isoforms, had a high rate of turnover. This developmental switch in NCAM isoform expression could be inhibited with Ca2+ channel blockers and inhibitors of protein kinase C. Taken together, these results suggest that Ca2+ ions and protein kinase C are involved in a second messenger cascade coupling membrane depolarization with transcriptional factors that regulate NCAM isoform synthesis and polysialylation.

Alternative Splicing↗
PubMed1996

Self-reinnervated cat medial gastrocnemius muscles. I. comparisons of the capacity for regenerating nerves to form enlarged motor units after extensive peripheral nerve injuries.

1. The aims of this study are to determine 1) whether regenerating motor axons have the capacity to form enlarged motor units (MUs) in muscles reinnervated by few motoneurons and 2) whether the type of nerve injury, repair, and/or growth environment affects this capacity. 2. MU innervation ratio (IR) was estimated by measuring isometric unit tetanic force in reinnervated cat medial gastrocnemius muscles 3-16 mo after denervation by either 1) crushing its nerve, 2) transecting the nerve and suturing the proximal end to the distal stump (N-N suture), or 3) transecting the nerve and suturing the proximal end directly to the muscle fascia (N-M suture). In addition, the number of regenerating axons was experimentally reduced by cutting one of two contributing ventral roots. 3. Muscles were reinnervated by 2-88% of their normal complement of MUs. Mean unit tetanic force increased as the number of reinnervated MUs decreased in reinnervated muscles after nerve crush or N-N suture, but not after N-M suture, even when few axons made functional connections. When the number of MUs was < 20% of normal, mean unit force was significantly higher in reinnervated muscles after nerve crush compared with muscle reinnervated after N-N suture. 4. The cross-sectional areas (CSAs) of all muscle fiber types were similar to normal in reinnervated muscles after nerve crush, but the CSAs of type IIa and IIb fibers were significantly smaller in muscles reinnervated after complete nerve transections (i.e., N-N or N-M sutures). 5. When MU force was normalized to mean muscle fiber CSA, cut motor axons displayed the same capacity to form enlarged MUs as crushed motor axons. The force of the MUs increased by as much as 5-8 times that of normal, provided the axons grew along the distal nerve stump (N-N suture). 6. Tetanic force increased in the normal order slow < fast-fatigue resistant < fast-fatigue intermediate = fast-fatigable. However, the increase in tetanic force of the slow (S) units was significantly larger than the corresponding increase of the more forceful fast (F) units. The disproportional increase in S and not F unit force, was primarily due to a significant decline in CSA of the type IIa and IIb muscle fibers. 7. The technique of glycogen depletion was used to count MU fibers to estimate the IR of MUs in 5 normal and 11 reinnervated muscles (7 N-N sutures, 4 N-M sutures). Unit tetanic force covaried with IR in both normal and reinnervated muscles. 8. These results show that regenerating axons have the same capacity as intact axons in partially denervated muscles to form enlarged MUs to compensate for a reduced number of functioning MUs. Only when axons regenerate in the absence of the distal nerve sheath is this capacity compromised.

Animals↗
PubMed1996

Self-reinnervated cat medial gastrocnemius muscles. II. analysis of the mechanisms and significance of fiber type grouping in reinnervated muscles.

1. The technique of glycogen depletion was used to determine whether regenerating motor axons reestablish the normal regionalization of motor units (MUs) in the cat medial gastrocnemius (MG) muscle, 2) whether the extent of clumping between MU fibers and/or type grouping of muscle fibers progressively increases with a decrease in reinnervated MU numbers, and 3) whether the pattern of innervation can explain why MUs fail to increase significantly in size when the cut nerve is sutured directly to the muscle, even when few axons make functional connections. 2. Distributions of MU fibers were analyzed in 5 normal and 14 reinnervated cat MG muscles 4.5-16 mo after sectioning of its nerve and suturing of the proximal end to the distal nerve sheaths (N-N suture) or directly to the muscle fascia (N-M suture). Muscle unit distributions were quantified according to location, territory size, density, and extent of clumping between fibers from the same MU. 3. Normal MU fibers were regionalized within five regions along the muscle's longitudinal and transverse axes. Reinnervated MUs were located within similar regions, indicating that regenerating axons follow the major proximal nerve branches to restore normal compartmentalization. 4. Muscle unit fibers were diffusely scattered within discrete MU territories in normal muscles. Territory size tended to increase with MU size, whereas density of muscle unit fibers within the territory decreased. 5. Territories increased with MU size after N-N suture but were smaller and showed little size variation after N-M suture. The extent of muscle unit fiber clumping was inversely related to the number of reinnervated MUs. On average, the extent of clumping was substantially higher in muscles reinnervated after N-M suture. These results indicate that distal nerve sheaths facilitate proximal axon branching, which establishes MU territory size. Once the territory is established, motor axons branch distally to increase MU size, which in turn compensates for reduced MU numbers. 6. Muscles reinnervated by < 80% of the MUs exhibited fiber type grouping of type I fibers, and on average the extent of clumping was substantially higher in muscles reinnervated after N-M suture. With less innervation, type grouping increased inversely with the number of reinnervated MUs. However, for a similar number of MUs, type I fiber type grouping was substantially higher in muscle reinnervated after N-M suture. Type grouping therefore reflects muscle unit fiber clumping under conditions where MU size increased (N-N suture) or MU territory size decreased (N-M suture).

Animals↗
PubMed1992

Proportional enlargement of motor units after partial denervation of cat triceps surae muscles.

1. To determine the capacity of motoneurons to increase their motor unit (MU) size by collateral sprouting and to assess this capacity in relation to the size of the motor nerve, we partially denervated soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) muscles in adult and neonatal cats. Isometric force and extracellular nerve potentials were recorded from > or = 7% of the remaining MUs, 2.5-18 mo later. S1 or L7 roots were sectioned unilaterally and the number of remaining MUs was quantified by use of charge and force measurements. 2. The mean unit force increased inversely with MU number in partially denervated muscles, but the increase was less than predicted for extensive denervations (> or = 90%). The same enlargement of MU size occurred whether muscles were partially denervated in neonatal or adult animals. 3. The force distribution of MUs in partially denervated muscles was similar to normal but was shifted to larger force values in direct proportion to the extent of partial denervation (PD). All MUs increased in size by the same factor to preserve the normal force distribution. 4. Normal size relationships among force, contractile speed, and axon potential amplitude were observed for MUs in partially denervated muscles. Because changes in muscle fiber size could not account for the increase in unit force, these data show that increase in MU size, with respect to unit force and innervation ratio (muscle fibers per motoneuron), is proportional to the size of the motor nerve. 5. Enlargement of MU size in partially denervated muscles did not have a retrograde effect on nerve fiber caliber because axon potential amplitude and conduction velocity were not changed after PD. 6. Under conditions of extensive PD (> 85%), regenerated nerves from the cut spinal root reinnervated the gastrocnemius muscles. It is likely that nerves supplied muscle fibers that were not innervated by sprouts from nerves in the uncut root as well as displacing sprouts from terminals in extensively enlarged MUs. 7. We conclude that all motoneurons within a motor pool compensate for partial nerve injuries by collateral sprouting and that enlargement of MU size is a function of motor nerve size, consistent with Henneman's size principle.

Action Potentials↗
PubMed1991

Properties of implanted electrodes for functional electrical stimulation.

Implanted wire electrodes are increasingly being used for the functional electrical stimulation of muscles in partially paralysed patients, yet many of their basic characteristics are poorly understood. In this study we investigated the selectivity, recruitment characteristics and range of control of several types of electrode in triceps surae and plantaris muscles of anaesthetized cats. We found that nerve cuffs are more efficient and selective (i.e., cause less stimulus spread to surrounding muscles) than intramuscular electrodes. Bipolar intramuscular stimulation was more efficient and selective than monopolar stimulation, but only if the nerve entry point was between the electrodes. Monopolar electrodes are efficient and selective if located close to the nerve entry point, but their performance declines with distance from it. Nonetheless, for a variety of reasons monopolar stimulation provides the best compromise in many current applications. Short duration pulses offer the best efficiency (least charge per pulse to elicit force) but high peak currents, increasing the risk of electrode corrosion and tissue damage. Electrode size has little effect on recruitment and should therefore be maximised because this minimises current density.

Action Potentials↗
PubMed1988

[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: absence of a selective increase in putative calcium channels in cardiomyopathic hearts.

The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM 9), 64(14) and 69(10) fmol.mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.

Animals↗