AN INVESTIGATION OF THE POSSIBLE ROLE OF PHOSPHOINOSITIDES AS REGULATORS OF ACTION POTENTIALS BY STUDYING THE EFFECT OF ELECTRICAL STIMULATION, TETRODOTOXIN AND CINCHOCAINE ON PHOSPHOINOSITIDE LABELLING BY32P IN RABBIT VAGUS

1972 ◽  
Vol 19 (5) ◽  
pp. 1233-1240 ◽  
Author(s):  
J. G. Salway ◽  
I. E. Hughes
Author(s):  
Q. Bone

INTRODUCTIONBoth the inner and outer epithelia of salps propagate action potentials (Mackie & Bone, 1977). Skin pulses in the outer epithelium underlying the test (OSPs) evoked by mechanical or electrical stimulation of the epithelium ‘enter’ the brain and may alter the regular rhythmic locomotor activity (Mackie & Bone, 1977; Anderson et al. 1979). The route of'entry’ has not been determined, but has been assumed to be via the axons of the scattered mechanoreceptor sensory cells lying in the outer epithelium. The OSP system would thus operate to extend the sensory field of such cells, as in the appendicularian Oikopleura (Bone & Mackie, 1975; Bone & Ryan, 1979) where two sensory cells are coupled to a conducting epithelium.Salps alternate generations between the solitary asexual oozooid, and the aggregated sexual blastozooids (budded from the stolon of the oozooid). The linked blastozooids form chains, along which OSPs pass to regulate the locomotor behaviour of individual zooids in the chain. The zooids are not linked by gap junctions, and OSPs pass along the chain in a complex.manner, involving alternating epithelioneural and neuroepithelial synapses (Bone, Anderson & Pulsford, 1980; Anderson & Bone, 1980). The OSP system of the oozooid generation is less well understood, although it is known that OSPs in the outer epithelium of the oozooid propagate into the stolon, where they have been studied by Anderson (1979). This paper shows that oozooids possess a similar system of neuroepithelial synapses to that of blastozooids, and that these ‘ drive’ OSPs in the same way as occurs during the regenerative transmission of OSPs along the blastozooid chain.


Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.


1984 ◽  
Vol 62 (1) ◽  
pp. 153-156 ◽  
Author(s):  
Archana Chaudhry ◽  
John W. Downie ◽  
Thomas D. White

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin–luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.


1980 ◽  
Vol 58 (7) ◽  
pp. 760-765 ◽  
Author(s):  
Eiji Kamitsubo

Three or four parallel fibrils of ca. 0.1 μm in width attached to each file of chloroplasts in intact internodal cells generate the motive force for cytoplasmic streaming. Experimental evidence for this conclusion is drawn from experiments in which fibrillar motion and streaming are interrupted by centrifugation, microbeam irradiation, and electrical stimulation. The role of Pb2+ in preventing cessation of cytoplasmic streaming after electrical stimulation is interpreted in terms of localized changes in viscosity of the cytoplasm.


1988 ◽  
Vol 118 (3) ◽  
pp. 471-483 ◽  
Author(s):  
L. M. Voloschin ◽  
E. Décima ◽  
J. H. Tramezzani

ABSTRACT Electrical stimulation of the XIII thoracic nerve (the 'mammary nerve') causes milk ejection and the release of prolactin and other hormones. We have analysed the route of the suckling stimulus at the level of different subgroups of fibres of the teat branch of the XIII thoracic nerve (TBTN), which innervates the nipple and surrounding skin, and assessed the micromorphology of the TBTN in relation to lactation. There were 844 ± 63 and 868 ± 141 (s.e.m.) nerve fibres in the TBTN (85% non-myelinated) in virgin and lactating rats respectively. Non-myelinated fibres were enlarged in lactating rats; the modal value being 0·3–0·4 μm2 for virgin and 0·4–0·5 μm2 for lactating rats (P > 0·001; Kolmogorov–Smirnov test). The modal value for myelinated fibres was 3–6 μm2 in both groups. The compound action potential of the TBTN in response to electrical stimulation showed two early volleys produced by the Aα- and Aδ-subgroups of myelinated fibres (conduction velocity rate of 60 and 14 m/s respectively), and a late third volley originated in non-myelinated fibres ('C') group; conduction velocity rate 1·4 m/s). Before milk ejection the suckling pups caused 'double bursts' of fibre activity in the Aδ fibres of the TBTN. Each 'double burst' consisted of low amplitude action potentials and comprised two multiple discharges (33–37 ms each) separated by a silent period of around 35 ms. The 'double bursts' occurred at a frequency of 3–4/s, were triggered by the stimulation of the nipple and were related to fast cheek movements visible only by watching the pups closely. In contrast, the Aα fibres of the TBTN showed brief bursts of high amplitude potentials before milk ejection. These were triggered by the stimulation of cutaneous receptors during gross slow sucking motions of the pup (jaw movements). Immediately before the triggering of milk ejection the mother was always asleep and a low nerve activity was recorded in the TBTN at this time. When reflex milk ejection occurred, the mother woke and a brisk increase in nerve activity was detected; this decreased when milk ejection was accomplished. In conscious rats the double-burst type of discharges in Aδ fibres was not observed, possibly because this activity cannot be detected by the recording methods currently employed in conscious animals. During milk ejection, action potentials of high amplitude were conveyed in the Aα fibres of the TBTN. During the treading time of the stretch reaction (SR), a brisk increase in activity occurred in larger fibres; during the stretching periods of the SR a burst-type discharge was again observed in slow-conducting afferents; when the pups changed nipple an abrupt increase in activity occurred in larger fibres. In summary, the non-myelinated fibres of the TBTN are increased in diameter during lactation, and the pattern of suckling-evoked nerve activity in myelinated fibres showed that (a) the double burst of Aδ fibres, produced by individual sucks before milk ejection, could be one of the conditions required for the triggering of the reflex, and (b) the nerve activity displayed during milk-ejection action may result, at least in part, from 'non-specific' stimulation of cutaneous receptors. J. Endocr. (1988) 118, 471–483


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Troy Hendrickson ◽  
William Perez ◽  
Vincent Provasek ◽  
Francisco J Altamirano

Patients with Autosomal Dominant Polycystic Kidney disease (ADPKD) have multiple cardiovascular manifestations, including increased susceptibility to arrhythmias. Mutations in polycystin-1 (PC1) encoding gene accounts for 85% cases of ADPKD, whereas mutations in polycystin-2 (PC2) only accounts for 15%. In kidney cells, PC1 interacts with PC2 to form a protein complex at the primary cilia to regulate calcium influx via PC2. However, cardiomyocytes are non-ciliated cells and the role of both PC1 and PC2 in atrial cardiomyocytes remains unknown. We have previously demonstrated that PC1 regulates action potentials and calcium handling to fine-tune ventricular cardiomyocyte contraction. Here, we hypothesize that PC1 regulates action potentials and calcium handling in atrial cardiomyocytes independent of PC2 actions. To test this hypothesis, we differentiated human induced pluripotent stem cells (iPSC) into atrial cardiomyocytes (iPSC-aCM) using previously published protocols. To determine the contribution of PC1/PC2 in atrial excitation-contraction coupling, protein expression was knocked down utilizing specific siRNA constructs, for each protein, or a universal control siRNA transfected using lipofectamine RNAiMAX. We measured action potentials using the potentiometric dye FluoVolt and intracellular calcium with Fura-2 AM or Fluo-4. Changes in fluorescence were monitored using a multiwavelength IonOptix system. iPSC-aCM were paced at 2 Hz to synchronize the beating pattern using field electrical stimulation. Our data shows that PC1 ablation significantly decreased action potential duration at 50% and 80% of repolarization, by 24% and 23%, respectively. Moreover, we observed that PC1 knockdown significantly reduced calcium transient amplitude elicited by field electrical stimulation without changes in calcium transient decay. Interestingly, PC2 knockdown did not modify calcium transients in atrial cardiomyocytes (iPSC-aCM). Our data suggest that PC1 regulates atrial excitation-contraction coupling independent of PC2 actions. This study warrants further investigation into atrial dysfunction in ADPKD patients with PC1 mutations.


1982 ◽  
Vol 242 (5) ◽  
pp. C366-C372 ◽  
Author(s):  
D. F. Wilson

The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.


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