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Autonomous Activity (autonomous + activity)
Selected AbstractsA molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease,MOVEMENT DISORDERS, Issue S1 2010C. Savio Chan PhD Abstract Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. There is no cure or proven strategy for slowing the progression of the disease. Although there are signs of pathology in many brain regions, the core symptoms of PD are attributable to the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. A potential clue to the vulnerability of these neurons is an increasing reliance with age upon L-type Ca2+ channels with a pore-forming Cav1.3 subunit to support autonomous activity. This reliance could pose a sustained stress on mitochondrial ATP generating oxidative phosphorylation, accelerating cellular aging and death. Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L-type Ca2+ channel independent mechanism to generate autonomous activity. This "rejuvenation" confers protection against toxins that produce experimental Parkinsonism, pointing to a potential neuroprotective strategy for PD. Their decades-long track record of safe use in the treatment of hypertension makes dihydropyridines particularly attractive as a therapeutic tool in PD. © 2010 Movement Disorder Society [source] Comparison study of autonomous activity in bladders from normal and paraplegic rats,,NEUROUROLOGY AND URODYNAMICS, Issue 4 2006Thomas Gevaert Abstract Aim To identify differences in the pattern of pressure generated by isolated bladders from normal and paraplegic rats. Materials and Methods Nine female Wister rats were made paraplegic by spinal cord transsection at the vertebral level T8-T9 and sacrificed between D21 and D28. A further group (n,=,9) was used as a control group. Each bladder was excised and placed in an organ bath where intravesical pressures were measured. Pressure changes were divided in two well-defined groups: macro-transients and spikes. The effects of intravesical volume load and muscarinic (M) agonists were studied. Results We demonstrated a higher frequency, a longer duration, and a higher variance of duration in macro-transients in the neurogenic group. Intravesical volume load influenced the amplitude and frequency of macro-transients in both groups similarly. The effects of the muscarinic (M2)-selective agonist arecaïdine were different in neurogenic bladder; the effects of the non-selective muscarinic (M)-agonist carbachol were similar in both groups. Conclusion We showed that the pattern of autonomous activity was significantly different between normal and neurogenic rat bladders. We also found evidence for alterations in the muscarinic response of isolated neurogenic rat bladders. This model offers an exciting new research tool to evaluate the detrusor activity in neurogenic and normal conditions. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Intrinsic properties and mechanisms of spontaneous firing in mouse cerebellar unipolar brush cellsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Marco J. Russo Neuronal firing patterns are determined by the cell's intrinsic electrical and morphological properties and are regulated by synaptic interactions. While the properties of cerebellar neurons have generally been studied in much detail, little is known about the unipolar brush cells (UBCs), a type of glutamatergic interneuron that is enriched in the granular layer of the mammalian vestibulocerebellum and participates in the representation of head orientation in space. Here we show that UBCs can be distinguished from adjacent granule cells on the basis of differences in membrane capacitance, input resistance and response to hyperpolarizing current injection. We also show that UBCs are intrinsically firing neurons. Using action potential clamp experiments and whole-cell recordings we demonstrate that two currents contribute to this property: a persistent TTX-sensitive sodium current and a ruthenium red-sensitive, TRP-like cationic current, both of which are active during interspike intervals and have reversal potentials positive to threshold. Interestingly, although UBCs are also endowed with a large Ih current, this current is not involved in their intrinsic firing, perhaps because it activates at voltages that are more hyperpolarized than those associated with autonomous activity. [source] Regulation and function of Ca2+,calmodulin-dependent protein kinase II of fast-twitch rat skeletal muscleTHE JOURNAL OF PHYSIOLOGY, Issue 3 2007Adam J. Rose The activation and function of Ca2+,calmodulin-dependent kinase II (CaMKII) in contracting rat skeletal muscle was examined. The increase in autonomous activity and phosphorylation at Thr287 of CaMKII of gastrocnemius muscle in response to contractions in situ was rapid and transient, peaking at 1,3 min, but reversed after 30 min of contractions. There was a positive correlation between CaMKII phosphorylation at Thr287 and autonomous CaMKII activity. In contrast to the rapid and transient increase in autonomous CaMKII activity, the phosphorylation of the putative CaMKII substrate trisk95/triadin was rapid and sustained during contractions. There were no changes in CaMKII activity and phosphorylation or trisk95 phosphorylation in the resting contralateral muscles during stimulation. When fast-twitch muscles were contracted ex vivo, CaMKII inhibition resulted in a greater magnitude of fatigue as well as blunted CaMKII and trisk95 phosphorylation, identifying trisk95 as a physiological CaMKII substrate. In summary, skeletal muscle CaMKII activation was rapid and sustained during exercise/contraction and is mediated by factors within the contracting muscle, probably through allosteric activation via Ca2+,CaM. CaMKII may signal through trisk95 to modulate Ca2+ release in fast-twitch rat skeletal muscle during exercise/contraction. [source] | ||||||||||