Two Mutations of synaptic transmission in Drosophila

Evoked transmitter release is abnormal at the larval neuromuscular junctions of two Drosophila mutants. Following a single nerve impulse, the increased calcium conductance at the nerve terminal, which lasts for 1 ms in normal larvae, lasts for at least 60 ms in one mutant and several seconds in the other. Both mutations appear to affect the same gene on the X-chromosome. Normal larvae treated with 4-aminopyridine, a potassium channel blocking agent, mimic the abnormal synaptic transmission of one mutant. Normal larvae treated with tetraethylammonium, another potassium channel blocking agent, mimic the abnormal synaptic transmission of the other mutant. From these and other experiments, we suggest that the abnormal neuromuscular transmission in these mutants may be caused by defective potassium channels in the nerve terminal membrane.

Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.


1933 ◽  
Vol 26 (11) ◽  
pp. 1454-1460 ◽  
Author(s):  
W. Ross Ashby

In many ways in physiology and psychology one sees evidences of “patterns.” Sensory stimuli are usually received as a pattern and most motor responses take the form of a clear-cut pattern of movements. The majority of the reactions in the central nervous system are concerned with patterns of impulses rather than a single nerve impulse. It is suggested that when two patterns meet, the interaction is subject to two definite laws:— (1) Similar patterns integrate and become one pattern, the differences between them building up to a new pattern. (2) Dissimilar patterns are dealt with by the complete acceptance or establishment of one pattern and the total rejection of the other. Examples are given to illustrate these two laws. It is suggested that whether two patterns are treated as similar or dissimilar will depend on: (1) The nature of the patterns themselves and; (2) the state or type of the nervous system. It is suggested that in the neuroses, what is really happening is that the person is treating as dissimilar certain patterns which are usually considered to be similar. Clinical applications are discussed.


1978 ◽  
Vol 202 (1149) ◽  
pp. 527-532 ◽  

Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.


2002 ◽  
Vol 35 (3) ◽  
pp. 201-212 ◽  
Author(s):  
Birgitta Houltz ◽  
B[ouml ]rje Darp[ouml ] ◽  
Harry J.G.M. Crijns ◽  
Karl Swedberg ◽  
Per Blomstr[ouml ]m ◽  
...  

1990 ◽  
Vol 259 (2) ◽  
pp. H626-H634
Author(s):  
C. F. Starmer ◽  
V. V. Nesterenko ◽  
F. R. Gilliam ◽  
A. O. Grant

Models of ion channel blockade are frequently validated with observations of ionic currents resulting from electrical or chemical stimulation. Model parameters for some models (modulated receptor hypothesis) cannot be uniquely determined from ionic currents. The time course of ionic currents reflects the activation (fraction of available channels that conduct in the presence of excitation) and availability of channels (the ability of the protein to make a transition to a conducting conformation and where this conformation is not complexed with a drug). In the presence of a channel blocking agent, the voltage dependence of availability appears modified and has been interpreted as evidence that drug-complexed channels exhibit modified transition rates between channel protein conformations. Because blockade and availability both modify ionic currents, their individual contributions to macroscopic conductance cannot be resolved from ionic currents except when constant affinity binding to a bindable site is assumed. Experimental studies of nimodipine block of calcium channels and lidocaine block of sodium channels illustrate these concepts.


2008 ◽  
Vol 295 (1) ◽  
pp. F171-F178 ◽  
Author(s):  
Carmen M. Troncoso Brindeiro ◽  
Rachel W. Fallet ◽  
Pascale H. Lane ◽  
Pamela K. Carmines

We previously reported an enhanced tonic dilator impact of ATP-sensitive K+ channels in afferent arterioles of rats with streptozotocin (STZ)-induced diabetes. The present study explored the hypothesis that other types of K+ channel also contribute to afferent arteriolar dilation in STZ rats. The in vitro blood-perfused juxtamedullary nephron technique was utilized to quantify afferent arteriolar lumen diameter responses to K+ channel blockers: 0.1–3.0 mM 4-aminopyridine (4-AP; KV channels), 10–100 μM barium (KIR channels), 1–100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of KIR channels), 100 nM apamin (SKCa channels), and 1 mM tetraethylammonium (TEA; BKCa channels). In kidneys from normal rats, 4-AP, TEA, and Ba2+ reduced afferent diameter by 23 ± 3, 8 ± 4, and 18 ± 2%, respectively, at the highest concentrations employed. Neither TPQ nor apamin significantly altered afferent diameter. In arterioles from STZ rats, a constrictor response to TPQ (22 ± 4% decrease in diameter) emerged, and the response to Ba2+ was exaggerated (28 ± 5% decrease in diameter). Responses to the other K+ channel blockers were similar to those observed in normal rats. Moreover, exposure to either TPQ or Ba2+ reversed the afferent arteriolar dilation characteristic of STZ rats. Acute surgical papillectomy did not alter the response to TPQ in arterioles from normal or STZ rats. We conclude that 1) KV, KIR, and BKCa channels tonically influence normal afferent arteriolar tone, 2) KIR channels (including Kir1.1 and/or Kir3.x) contribute to the afferent arteriolar dilation during diabetes, and 3) the dilator impact of Kir1.1/Kir3.x channels during diabetes is independent of solute delivery to the macula densa.


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