Most axons in the mammalian brain are unmyelinated and thin with pre-synaptic specializations (boutons) along their entire paths. The parallel fibers in the cerebellum are examples of such axons. Unlike most thin axons they have only one branch point. The granule cell soma, where they originate, can fire bursts of action potentials with spike intervals of about 2 ms. An important question is whether the axons are able to propagate spikes with similarly short intervals. By using extracellular single-unit and population-recording methods we showed that parallel fibers faithfully conduct spikes at high frequencies over long distances. However, when adding 20 microm ZD7288 or 1 mm Cs(+), or reducing the temperature from 35 to 24 degrees C, the action potentials often failed even when successfully initiated. Ba(2+)(1 mm), which blocks Kir channels, did not reproduce these effects. The conduction velocity was reduced by ZD7288 but not by Ba(2+). This suggests that the parallel fibers have an H-current that is active at rest and that is important for their frequency-following properties. Interestingly, failures occurred only when the action potential had to traverse the axonal branch point, suggesting that the branch point is the weakest point in these axons.
At sites of purinergic neurotransmission, synaptic ecto-ATPase is believed to limit the actions of ATP following its neural release. However, details of the modulation by this enzyme of the ATP-mediated conductance change and the possible mechanisms mediating this modulation remain unelucidated. We have addressed these issues by studying the effect of ARL 67156, a selective ecto-ATPase inhibitor, on ATP-mediated electrical and contractile activity in the sympathetically innervated guinea-pig vas deferens. ARL 67156 at 100 μM significantly potentiated the amplitude of spontaneous excitatory junction potentials (SEJPs) by 81.1% (P < 0.01) and prolonged their time courses (rise time by 49.7%, decay time constant by 38.2%; P < 0.01). Moreover, the frequency of occurrence of SEJPs was strikingly increased (from 0.28 ± 0.13 to 0.90 ± 0.26 Hz; P < 0.01), indicating an additional, primarily presynaptic, effect of ecto-ATPase inhibition. The frequency of occurrence of discrete events (DEs), which represent nerve stimulation-evoked quantal release of neurotransmitter, was also increased (∼6-fold; P < 0.01), along with the appearance of DEs at previously 'silent' latencies. Purinergic contractions of the vas deferens were potentiated significantly (P < 0.01) by ARL 67156; these potentiated contractions were suppressed by the A1 agonist adenosine (P < 0.01) but left unaffected by the A1 antagonist 8-phenyltheophylline (8-PT). Our results indicate (i) that ecto-ATPase activity, in addition to modulating the ATP-mediated postjunctional conductance change, may regulate transmitter release prejunctionally under physiological conditions, and (ii) that the prejunctional regulation may be mediated primarily via presynaptic P2X, rather than A1, receptors.
We have studied the effects of 1-heptanol and nifedipine on noradrenaline (NA)-induced contractions in order to explore the role of gap junctions and their interactions with L-type Ca 2+ channel mediated [Ca 2+ ]o entry in the generation of NA-induced contractions in the rat vas deferens. Application of 20 μM NA to rat vas deferens resulted in contractions with three different components, an initial phasic component followed by a tonic component overlapped with an oscillatory component. Heptanol (0.01-2 mM) induced a concentration dependent reduction of the contractions. 2 mM heptanol reduced the phasic component by 32.9 ± 4.4% and the tonic component by 93.8 ± 1.9% of control, while the oscillatory component was completely abolished (n=7). Nifedipine (2 μM) reduced the phasic component by 34.5 ± 4.1% and the tonic component by 89.5 ± 3.8% of control and abolished the oscillatory component (n=6). In the presence of heptanol and nifedipine together, the phasic component was reduced by 61.3 ± 8.3% and the tonic component by 94.5 ± 1.0% of control. The oscillatory component was completely abolished (n=6). These results allow the conclusion that phasic contraction is mainly due to the direct action of NA, independent of gap junctions, while the tonic and oscillatory contractions may depend significantly on cell-to-cell communication. These in turn may depend critically on the availability of extracellularly derived Ca 2+ .
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