Mechanism of action of galanin on myenteric neurons

1988 ◽  
Vol 60 (3) ◽  
pp. 966-979 ◽  
Author(s):  
K. Tamura ◽  
J. M. Palmer ◽  
C. K. Winkelmann ◽  
J. D. Wood
Keyword(s):  
Mechanism Of Action ◽  
Reversal Potential ◽  
Input Resistance ◽  
Equilibrium Potential ◽  
Bathing Medium ◽  
Simultaneous Application ◽  
Membrane Hyperpolarization ◽  
K Channels ◽  
Myenteric Neurons ◽  
Spike Initiation

1. Conventional intracellular recording methods were used to investigate the mechanism of action of galanin on electrical behavior of AH/type 2 myenteric neurons in the guinea pig small intestine. 2. The overall action of galanin was inhibitory and consisted of membrane hyperpolarization, decreased input resistance, and suppression of excitability. 3. The action of galanin was on the somatic membrane. There were no effects on spike initiation or propagation velocity in the processes. 4. The reversal potential for the hyperpolarizing action of galanin was near the estimated K+ equilibrium potential and was dependent on the concentration of K+ in the bathing medium. 5. Treatment with tetraethylammonium (TEA) broadened the action-potential and enhanced long-lasting hyperpolarizing after-potentials (AH). Application of galanin or depletion of Ca2+ in the bathing medium offset the effects of TEA on the spike and the AH. Galanin or reduced Ca2+ had the same effect when both TEA and tetrodotoxin (TTX) were present. 6. Simultaneous application of TEA and 4-aminopyridine (4-AP) evoked spontaneous spike discharge with broadened spikes and enhanced AH. This activity was suppressed by galanin. 7. Intrasomatic injection of Cs+ in the presence of TTX appeared to abolish all K+ conductances leaving pure Ca2+ spikes in response to depolarizing current pulse. Galanin abolished these Ca2+ spikes. 8. The results suggest two major mechanisms of action for galanin. One is to open K+ channels, decrease input resistance, and hyperpolarize the membrane toward EK+. The second is blockade of voltage gated Ca2+ channels and suppression of the AH by indirect prevention of opening of Ca2+-dependent K+ channels.

Cholecystokinin-gated currents in neurons of the rat solitary complex in vitro

1993 ◽  
Vol 70 (6) ◽  
pp. 2584-2595 ◽  
Author(s):  
P. Branchereau ◽  
J. Champagnat ◽  
M. Denavit-Saubie
Keyword(s):  
Voltage Clamp ◽  
Potassium Current ◽  
Reversal Potential ◽  
Input Resistance ◽  
Calcium Currents ◽  
Equilibrium Potential ◽  
Potassium Ions ◽  
Nernst Equation ◽  
Membrane Hyperpolarization ◽  
Cckb Receptor

1. Ionic conductances controlled by type A and type B cholecystokinin (CCK) receptors were studied in neurons of the rat nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNV), using intracellular and whole-cell patch clamp recordings in current or voltage clamp configuration during bath application of agonists (CCK8, CCK4, BC 264) and antagonists. 2. CCKA receptor-related inhibition was associated with a membrane hyperpolarization and a decrease in input resistance that developed 2-6 min after the arrival of drug into the extracellular medium. These effects were induced by 5 nM CCK8 but not BC 264 and they were blocked by the CCKA antagonist, L-364,718, but not by the CCKB antagonist, L-365,260. 3. CCKA receptor-related inhibition was generated by a potassium current that reversed at a reversal potential E(rev) of -73 +/- 1 (mean +/- SE) mV with bathing potassium concentration [K+]o = 6 mM and at -88 +/- 1 with [K+]o = 3 mM, in agreement with the Nernst equation for potassium ions. 4. CCKB receptor-related excitation was associated with a membrane depolarization and an increase of the input resistance induced by the following agonists at threshold concentrations: CCK8 (0.2 nM) > or = BC 264 (0.4 nM) > CCK4 (10.9 nM). The increase of input resistance was abolished by L-365,260 and was maintained after blockade of the CCKA current by L-364,718. 5. CCKB receptor-related excitation, in the neurons (30% of cases) in which clear response reversal was observed, appeared to be generated by a decrease of a potassium conductance. Responses showed a reversal potential E(rev) of -68 +/- 4 mV with [K+]o = 6 mM and -89 +/- 1 mV with [K+]o = 3 mM, verifying predictions from the Nernst equation applied to potassium ions. However, in 70% of cases, clear reversal was not observed at membrane potentials negative to the theoretical potassium equilibrium potential EK. 6. In voltage clamp studies, CCK8 induced a 181 +/- 17 pA inward current associated with a 26 +/- 4% decrease in the instantaneous current (I(ins)) generated by hyperpolarizing voltage steps. This effect on I(ins) was demonstrated in the absence of effects on the outward noninactivating potassium current (IM) and on the inward noninactivating cationic current (IQ). 7. CCKB receptor-mediated excitation was not suppressed by cobalt, a blocker of calcium currents, and was not associated with a change of the calcium-dependent potassium current (IK(Ca)).(ABSTRACT TRUNCATED AT 400 WORDS)

Electrical properties of frog motoneurons in the in situ spinal cord

1976 ◽  
Vol 39 (3) ◽  
pp. 459-473 ◽  
Author(s):  
P. C. Magherini ◽  
W. Precht
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Electrical Properties ◽  
Rana Temporaria ◽  
Reversal Potential ◽  
Input Resistance ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Spike Initiation

Electrical properties of the spinal motoneurons of Rana temporaria and R. esculenta were investigated in the in situ spinal cord at 20-22 degrees C by means of intracellular recording and current injection. Input resistance values depended on the method of measurement in a given cell but were generally inversely related to axon conduction velocity. The membrane-potential response to a subthreshold current pulse was composed of at least two exponentials with mean time constants of 2.5 and 20 ms. The membrance potential reached by the peak of a spike depended on the mode of spike initiation and membrane potential. Preceding a suprathreshold depolarization by a hyperpolarizing pulse could delay and eliminate spike initiation, similar to effects reported in certain invertebrate neurons. Antidromic invasion frequently failed in motoneurons of normal resting potential. Antidromic spike components (m,IS, SD) were similar to those of cat motoneurons. The delayed depolarization and the long afterhyperpolarization following an antidromic spike had many properties in common with the analogous afterpotentials of cat motoneurons. The reversal potential of the short afterhyperpolarization occurring immediately after the spike varied with resting potential and could not be used to determine potassium equilibrium potential. Sustained rhythmic firing could be evoked by continuous synaptic drive or long pulses of injected current. The plot of firing rate versus current strength had a substantial linear region. Both steady firing and adaptation properties varied markedly with motoneuron input resistance.

Angiotensin II Induces Calcium-Dependent Rhythmic Activity in a Subpopulation of Rat Hypothalamic Median Preoptic Nucleus Neurons

2005 ◽  
Vol 93 (4) ◽  
pp. 1970-1976 ◽  
Author(s):  
David Spanswick ◽  
Leo P. Renaud
Keyword(s):  
Angiotensin Ii ◽  
Reversal Potential ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Bathing Medium ◽  
Membrane Hyperpolarization ◽  
Median Preoptic Nucleus

Whole cell patch-clamp recordings revealed a subpopulation (16%, n = 18/112) of rat median preoptic nucleus (MnPO) neurons responded to bath-applied angiotensin II (Ang II; 100 nM to 5 μM; 30–90 s) with a prolonged TTX-resistant membrane depolarization and rhythmic bursting activity. At rest, cells characteristically displayed relatively low input resistance and negative resting potentials. Ang-II-induced responses featured increased input resistance, a reversal potential of −95 ± 2 mV, an increase in action potential duration from 2.9 ± 0.5 to 4.3 ± 0.8 ms, and the appearance of a rebound excitation at the offset of membrane responses to hyperpolarizing current injection. The latter was sensitive to Ni2+ (0.5–1 mM; n = 5), insensitive to extracellular Cs+ (1 mM, n = 7), and intracellular QX-314 (4 mM, n = 5), consistent with activation of a T-type Ca2+ conductance. Coincident with the Ang-II-induced depolarization was the appearance of rhythmic depolarizing shifts at a frequency of 0.14 ± 0.09 Hz with superimposed bursts of 4–22 action potentials interspersed with silent periods persisting for >1 h after washout. These TTX-resistant depolarizing shifts increased in amplitude and decreased in frequency with membrane hyperpolarization with activity ceasing beyond approximately –80mV, and were abolished in low-Ca2+/high-Mg2+ bathing medium ( n = 6), Co2+ (1 mM; n = 6), or Ni2+ (0.5–1 mM; n = 8). Thus in a subpopulation of MnPO neurons, Ang II induces “pacemaker-like” activity by reducing a K+-dependent leak conductance that contributes to resting membrane potential and promoting of Ca2+-dependent regenerative auto-excitation mediated, in part, by a T-type Ca2+ conductance.

Ca2+-activated Cl− current in cultured myenteric neurons from murine proximal colon

2003 ◽  
Vol 284 (4) ◽  
pp. C839-C847 ◽  
Author(s):  
Sok Han Kang ◽  
Pieter Vanden Berghe ◽  
Terence K. Smith
Keyword(s):  
Membrane Potential ◽  
Channel Blocker ◽  
Reversal Potential ◽  
Outward Current ◽  
Proximal Colon ◽  
Time Dependent ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Myenteric Neurons ◽  
Whole Cell Patch Clamp

Whole cell patch-clamp recordings were made from cultured myenteric neurons taken from murine proximal colon. The micropipette contained Cs+ to remove K+ currents. Depolarization elicited a slowly activating time-dependent outward current ( I tdo), whereas repolarization was followed by a slowly deactivating tail current ( I tail). I tdo and I tail were present in ∼70% of neurons. We identified these currents as Cl− currents ( I Cl), because changing the transmembrane Cl− gradient altered the measured reversal potential ( E rev) of both I tdo and I tail with that for I tailshifted close to the calculated Cl− equilibrium potential ( E Cl). I Cl are Ca2+-activated Cl− current [ I Cl(Ca)] because they were Ca2+dependent. E Cl, which was measured from the E rev of I Cl(Ca) using a gramicidin perforated patch, was −33 mV. This value is more positive than the resting membrane potential (−56.3 ± 2.7 mV), suggesting myenteric neurons accumulate intracellular Cl−. ω-Conotoxin GIVA [0.3 μM; N-type Ca2+ channel blocker] and niflumic acid [10 μM; known I Cl(Ca) blocker], decreased the I Cl(Ca). In conclusion, these neurons have I Cl(Ca) that are activated by Ca2+entry through N-type Ca2+ channels. These currents likely regulate postspike frequency adaptation.

TRH-induced membrane hyperpolarization in rat clonal anterior pituitary cells

1985 ◽  
Vol 248 (1) ◽  
pp. E64-E69
Author(s):  
S. Ozawa
Keyword(s):  
Reversal Potential ◽  
Membrane Conductance ◽  
Gh3 Cells ◽  
Ionophore A23187 ◽  
Pituitary Cells ◽  
Bathing Medium ◽  
Membrane Hyperpolarization ◽  
K Concentration ◽  
The Relationship ◽  
Reversal Potentials

Thyrotropin-releasing hormone (TRH) induces biphasic membrane potential changes, a transient hyperpolarization followed by a prolonged enhancement of the generation of action potentials in the clonal GH3 pituitary cell. The nature of the TRH-induced hyperpolarization was studied in Cl--free solutions. Among various test substances, only TRH and its analogue, which stimulates the release of prolactin from the GH3 cells, were capable of inducing the transient membrane hyperpolarization. The Ca2+ ionophore A23187 also caused a transient hyperpolarization accompanied by an increase in the membrane conductance, although it failed to mimic the late facilitation of spike generation. The reversal potential of the TRH-induced hyperpolarization was identical with that induced by A23187. Reduction of the K+ concentration of the bathing medium caused a similar shift of both these reversal potentials toward a more hyperpolarized level. Injection of the Ca2+-chelator EGTA into the cell suppressed both TRH and Ca2+ ionophore-induced hyperpolarizations. These results suggest that TRH mobilizes the cellular-bound Ca, which in turn activates Ca2+-mediated K+ channels, thus causing the transient membrane hyperpolarization. The relationship between the membrane hyperpolarization and the TRH-stimulated hormone release is discussed.

Synaptic behavior of myenteric neurons in guinea pig distal colon

1988 ◽  
Vol 255 (2) ◽  
pp. G184-G190 ◽  
Author(s):  
P. R. Wade ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Input Resistance ◽  
Distal Colon ◽  
Bathing Medium ◽  
Myenteric Neurons ◽  
Fiber Tracts ◽  
Slow Rise ◽  
Domain 3 ◽  
Myenteric Ganglia

Intracellular recording methods were used in vitro to analyze the synaptic behavior of neurons in myenteric ganglia of guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs) were observed in a variety of types of colonic neurons. Both spontaneous and stimulus-evoked EPSPs were abolished or suppressed by addition of hexamethonium, tetrodotoxin, or elevation of Mg2+ and reduction of Ca2+ in the bathing medium. Individual neurons usually received inputs from several fiber tracts and multiple EPSPs were sometimes evoked by electrical stimulation of single-fiber tracts. Stimulus-evoked fast EPSPs were always of greater amplitude, longer duration, and longer decay time than were spontaneous fast EPSPs in the same neurons. No rundown of the fast EPSPs occurred during prolonged stimulation at frequencies up to 10 Hz. Repetitive stimulation evoked slow depolarizing potentials (slow EPSPs) in 25% of the neurons. Characteristics of the slow EPSPs were 1) slow rise times, 2) duration in the seconds time domain, 3) enhanced excitability, 4) increased input resistance, and 5) reduction of hyperpolarizing after-potentials. In general, the variety of synaptic potentials and the properties of the events were the same as found in myenteric neurons of the guinea pig small bowel. Compared with synaptic behavior of small intestinal myenteric neurons, the notable differences were absence of the rundown phenomenon for fast EPSPs in the colonic neurons and a greater incidence of spontaneously occurring fast EPSPs.

Potassium distribution and membrane potential of sensory neurons in the leech nervous system

1984 ◽  
Vol 51 (4) ◽  
pp. 689-704 ◽  
Author(s):  
W. R. Schlue ◽  
J. W. Deitmer
Keyword(s):  
Nervous System ◽  
Membrane Potential ◽  
Sensory Neurons ◽  
Membrane Resistance ◽  
Equilibrium Potential ◽  
Bathing Medium ◽  
Membrane Hyperpolarization ◽  
K Concentration ◽  
Intracellular K Activity ◽  
K Activity

The intracellular K activity (aKi) and membrane potential of sensory neurons in the leech central nervous system were measured in normal and altered external K+ concentrations, [K+]o, using double-barreled, liquid ion-exchanger microelectrodes. In control experiments membrane potential measurements were made using potassium chloride-filled single-barreled microelectrodes. All values are means +/- SD. At the normal [K+]o (4 mM) the mean aKi of all cells tested was 72.6 +/- 10.6 mM (n = 40) and the average membrane potential was -47.3 +/- 5.2 mM (n = 40). When measured with single-barreled microelectrodes, the membrane potential averaged -45.3 +/- 2.9 mV (n = 12). Assuming an intracellular K+ activity coefficient of 0.75, the intracellular K+ concentration of sensory neurons would be 96.8 +/- 14.1 mM). With an extracellular K+ concentration of 5.8 mM in the intact ganglion compared to the K+ concentration of 4 mM in the bath, the K+ equilibrium potential was -71.5 mV. When the ganglion capsule was opened, the extracellular K+ concentrations in the ganglion were similar to that of the bathing medium and the calculated K+ equilibrium potential was -81 mV. The membrane of sensory neurons depolarized following the changes to elevated [K+]o (greater than or equal to 10-100 mM), whereas aKi changed only little or not at all. At very low [K+]o (0.2, 0 mM) aKi and membrane potential showed little short-term (less than 3 min) effect but began to change after longer exposure (greater than 3 min). Reduction of [K+]o from 4 to 0.2 mM (or 0 mM) produced first a slow, and then a more rapid decrease of aKi and membrane resistance, accompanied by a slow membrane hyperpolarization. Following readdition of normal [K+]o, the membrane first depolarized and then transiently hyperpolarized, eventually returning slowly to the normal membrane potential.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals The ionic basis of the receptor potential of frog taste cells induced by water stimuli.

1993 ◽  
Vol 174 (1) ◽  
pp. 1-17
Author(s):  
Y Okada ◽  
T Miyamoto ◽  
T Sato
Keyword(s):  
Basolateral Membrane ◽  
Reversal Potential ◽  
Receptor Potential ◽  
Input Resistance ◽  
Deionized Water ◽  
Glossopharyngeal Nerve ◽  
Equilibrium Potential ◽  
Induced Response ◽  
Control Value ◽  
Taste Cells

The ionic mechanism underlying the receptor potential induced by a deionized water stimulus was studied in frog taste cells with conventional microelectrodes. The taste cells located in the proximal portion of the tongue generated a depolarizing receptor potential which averaged 10mV in response to stimulation with deionized water. The cell membrane of the water-sensitive taste cell could be divided into the taste-receptive (apical) and basolateral membranes and the cells were classified into two types: Cl(-)-dependent and Cl(-)-independent. In Cl(-)-dependent cells whose input resistance was decreased or unchanged by deionized water, the magnitude of the water-induced depolarization decreased with an increase in concentration of superficial Cl- in contact with the receptive membrane and with addition of blockers of anion channels (0.1 mmol l-1 SITS and 0.1 mmol l-1 DIDS) to deionized water. The reversal potential for the depolarization in this type shifted according to the concentration of superficial Cl-. These properties of the responses were consistent with those of the glossopharyngeal nerve which innervates the taste disc. In Cl(-)-independent cells whose input resistance was increased by deionized water, the reversal potential was approximately equal to the equilibrium potential for K+ at the basolateral membrane. The water-induced response of the glossopharyngeal nerve was decreased to about 60% of the control value by addition of interstitial 2 mmol l-1 Ba2+. It is concluded that the water-induced receptor potential is produced by Cl- secretion through the taste-receptive membrane in about 70% of water-sensitive frog taste cells, while it is generated by an inhibition of the resting K+ conductance of the basolateral membrane in the remaining 30% of the cells.

Cholinergic features of photoreceptor synapses in Hermissenda

1979 ◽  
Vol 42 (1) ◽  
pp. 153-165 ◽  
Author(s):  
E. Heldman ◽  
Y. Grossman ◽  
T. P. Jerussi ◽  
D. L. Alkon
Keyword(s):  
Optic Tract ◽  
Reversal Potential ◽  
Input Resistance ◽  
Membrane Resistance ◽  
Electron Microscopic ◽  
Radioactive Label ◽  
Membrane Hyperpolarization ◽  
Neurotransmitter Substances ◽  
And Storage ◽  
Inhibitory Interactions

1. A number of observations, as listed below, suggested a cholinergic basis for inhibitory interactions between photoreceptors of the eye in the nudibranch mollusk Hermissenda crassicornis. 2. The isolated eyes synthesized and accumulated acetylcholine but not other putative neurotransmitter substances. Synthesis and accumulation were determined by electrophoretic separation of products that incorporated radioactive label. Electron microscopic visualization of clear round vesicles within the photoreceptors' somata and axon hillocks was consistent with synthesis and storage of acetylcholine within these cells. 3. Pharmacologic experiments indicated the presence of cholinergic receptors on the terminal branches of the photoreceptors, which are pre- and postsynaptic to each other. Carbachol or nicotine produced hyperpolarization of the photoreceptors' membrane accompanied by a reduction of the input resistance. The reversal potential of carbachol-induced hyperpolarization coincided with the reversal potentials of the IPSPs that followed, one for one, impulses of neighboring photoreceptors. Eserine often caused blockade of the IPSPs. This blockade was associated with substantial membrane hyperpolarization and reduction of membrane resistance. 4. Neuronal endings within the optic tract in the area of the photoreceptor's terminal branches stained for acetylcholinesterase. 5. The results of these different experiments, especially when considered together, strongly suggest, although by no means unequivocally demonstrate, that the neurotransmitter of the photoreceptors is acetylcholine.

Adrenergic receptors (α1 and α2) modulate different potassium conductances in sympathetic preganglionic neurons

1992 ◽  
Vol 70 (S1) ◽  
pp. S92-S97 ◽  
Author(s):  
Hiroe Inokuchi ◽  
Megumu Yoshimura ◽  
Canio Polosa ◽  
Syogoro Nishi
Keyword(s):  
Spinal Cord ◽  
Input Resistance ◽  
Equilibrium Potential ◽  
Extracellular Potassium ◽  
Thoracic Spinal Cord ◽  
Membrane Hyperpolarization ◽  
Sympathetic Preganglionic Neurons ◽  
Preganglionic Neurons ◽  
Thoracic Spinal ◽  
Spinal Cord Segment

Intracellular recordings were made from 168 sympathetic preganglionic neurons in the slice of the second or third thoracic spinal-cord segment of the adult cat to study the actions of noradrenaline on these neurons. Noradrenaline, applied by superfusion (0.5–50 μM), produced membrane depolarization in 73 neurons and membrane hyperpolarization in 39 neurons. In 26 neurons noradrenaline produced a biphasic response (depolarization–hyperpolarization or vice versa). The depolarization was blocked by prazosin, while the hyperpolarization was blocked by yohimbine. The noradrenaline-induced depolarization was associated with an increase in neuron input resistance, while the noradrenaline-induced hyperpolarization was associated with a decrease in neuron input resistance. Both responses decreased in amplitude with membrane hyperpolarization and were nullified at around the potassium equilibrium potential EK. The null potential of both responses became more and less negative with a decrease and an increase, respectively, in the extracellular potassium concentration. When the membrane potential was made more negative than EK, the noradrenaline-induced hyperpolarization reversed to depolarization in all cases, whereas in only 4 of 12 cases did the noradrenaline-induced depolarization reverse to hyperpolarization. These data suggest that the noradrenaline-induced depolarization is a result of a decrease, while the noradrenaline-induced hyperpolarization is a result of an increase in K+ conductance. Cobalt (2 mM), low calcium – high magnesium, and intracellular EGTA markedly reduced or abolished the noradrenaline-induced depolarization but had no significant effect on the noradrenaline-induced hyperpolarization. Barium (2 mM) depressed both responses. Tetraethylammonium (10–30 mM), 4-aminopyridine (3 mM), and cesium (2 mM) had no effect on either response. These data suggest that the noradrenaline-induced depolarization is a result of an inactivation of a background calcium-sensitive K+ conductance, while the noradrenaline-induced hyperpolarization is due to activation of a calcium-insensitive potassium conductance.Key words: K+ conductances, catecholamines, Ca2+ dependent, K+ current, spinal cord.

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