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L J Regan

Publications and source records attributed to L J Regan.

7 recordsLinked to original sources

Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin.

Block of Ca2+ channel current by dihydropyridines and by omega-conotoxin (omega-CgTx) was studied in a variety of freshly dissociated rat neurons. In most neurons, including those from dorsal root ganglia, sympathetic ganglia, spinal cord, cerebral cortex, and hippocampus, nitrendipine and omega-CgTx each blocked a fraction of the high-threshold current, but a substantial fraction of current remained even when the two blockers were applied together at saturating concentrations. An extreme case was cerebellar Purkinje neurons, in which very little current was blocked by either nitrendipine or omega-CgTx. These results demonstrate the existence in mammalian neurons of high-threshold channels that are resistant to both omega-CgTx and dihydropyridine blockers. Such channels might underlie instances of synaptic transmission and other processes that depend on Ca2+ entry but are not sensitive to these blockers.

Animals↗

Voltage-dependent calcium currents in Purkinje cells from rat cerebellar vermis.

Whole-cell patch clamp recording was used to characterize calcium currents in Purkinje cells dissociated from the cerebellar vermis of 1-3-week postnatal rats. A subset of Purkinje cells had a low-threshold, transient current similar to the T-type current in peripheral neurons. All Purkinje cells had a high-threshold, slowly inactivating current. Only a small component of the high-threshold current was sensitive to dihydropyridine (DHP) antagonists or to the dihydropyridine agonist BAY K8644. omega-Conotoxin had very little effect on the high-threshold current. The results suggest that these Purkinje cells have at least three types of calcium channels: T-type channels (present in only a fraction of cells), DHP-sensitive L-type channels (contributing a small fraction of the high-threshold current), and a predominant type of high-threshold channel that is pharmacologically distinct from L-type and N-type channels characterized in peripheral neurons.

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

Behavior, genetics and biochemistry of an allele of the mutant mouse spastic, spaAlb.

A new autosomal recessive mutation, characterized by an early defect in righting reflex and stiffened gait, progression to severe spasticity, tremor and rigidity, and death before weaning, appeared spontaneously on the C57BL/6 background. It was shown to be an allele of the mutant spastic spa, and shall be known as spaAlb. Mutant levels of [3H]strychnine binding are less than 10% of control levels in the brainstem and spinal cord. Autoradiographic examination of the distribution of [3H]strychnine binding sites in the mutant confirm a greatly reduced level of binding compared to control in all areas of the spinal cord, brainstem, and midbrain.

Alleles↗

Selective expression of endogenous lactose-binding lectins and lactoseries glycoconjugates in subsets of rat sensory neurons.

Cell-surface glycoconjugates and endogenous lectins have been implicated in cellular interactions that contribute to embryonic development. Functional subsets of primary sensory neurons in mammalian dorsal root ganglia (DRG) have been shown recently to express specific cell-surface oligosaccharide structures. We report here that endogenous lectins with affinity for sensory neuron glycoconjugates are also synthesized by subsets of DRG neurons and are present in the dorsal horn of the developing spinal cord. The distribution of two endogenous lactose-binding lectins, RL-14.5 and RL-29 (subunit Mrs of 14,500 and 29,000, respectively), was examined by immunoblotting and by immunocytochemistry in embryonic and postnatal rat DRG and spinal cord. The two lectins appear soon after the formation of the DRG and are present in the cell bodies and terminals of subsets of DRG neurons that also express cytoplasmic and cell-surface lactoseries glycoconjugates. RL-14.5 and RL-29 are present in overlapping, but not coincident, subsets of DRG neurons that project to the superficial dorsal horn of the spinal cord. In addition, RL-14.5, but not RL-29, is expressed in spinal motoneurons from embryonic day 14. The preferential localization of lactoseries glycoconjugates and lactose-binding lectins in the DRG and the dorsal horn of the spinal cord suggests that these complementary molecules contribute to the development and function of primary sensory neurons.

Animals↗

Two subtypes of sodium channel with tetrodotoxin sensitivity and insensitivity detected in denervated mammalian skeletal muscle.

The action potential (AP) in most nerve and muscle preparations depends upon nanomolar concentrations of the neurotoxins saxitoxin (STX) and tetrodotoxin (TTX). In some excitable tissues lacking mature innervation, a toxin-resistant AP has been described by electrophysiological results. However, multiple attempts to detect corresponding toxin-resistant Na channels with radiolabelled STX and TTX have been unsuccessful. We report here the detection of Na channels with low-affinity binding of STX and TTX, accounting for 50-60% of the Na channels in rat hindlimb muscle 4-5 days after denervation.

Action Potentials↗

Identification of two sodium channel subtypes in chick heart and brain.

Na+ channels in chick brain and heart have been directly compared by measuring binding of tritium-labeled saxitoxin ([3H]STX) to the two tissues under identical conditions. Maximum saturable uptake and toxin affinity were considerably less in chick heart than in chick brain, requiring the development of an assay method to resolve specific [3H]STX uptake in heart. With this method, binding to both preparations consisted of a specific saturable component and a linear nonspecific component. The equilibrium dissociation constant for [3H]STX measured in chick heart (6.2-8.8 nM) was 20-30 times higher than that measured in chick brain (0.3 nM). The dissociation rate for [3H]STX was only about twice as fast in heart as it was in brain, indicating that the decrease in toxin affinity in heart results predominantly from a slowed toxin association rate. The decreased affinity for [3H]STX found at the chick heart Na+ channel is compared with toxin-resistant Na+ channels in other preparations. The existence of two Na+ channel subtypes is proposed, with high affinity and low affinity for saxitoxin and tetrodotoxin; the significance of this classification is discussed.

Animals↗