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C Barajas-López

Publications and source records attributed to C Barajas-López.

At least 19 recordsLinked to original sources
PubMed2001

5-Hydroxytryptamine and atropine inhibit nicotinic receptors in submucosal neurons.

The whole-cell recording technique was used to investigate the pharmacological properties of acetylcholine-activated ion channels of cultured submucosal neurons from guinea-pig small intestine. Acetylcholine induced whole-cell membrane currents (I(ACh)) in a concentration-dependent manner (EC(50)=79 microM). I(ACh) exhibited strong inward rectification, had a reversal potential of +19+/-2 mV (Na(+) outside, Cs(+) inside), was reversibly inhibited in a concentration-dependent manner by hexamethonium (EC(50)=5 microM) and atropine (EC(50)=1.6 microM), and was unaffected by alpha-bungarotoxin (30 nM). Atropine was less potent in inhibiting the currents induced by 30 microM acetylcholine than those induced by 1 mM acetylcholine. I(ACh) was mimicked by the current induced by nicotine (I(Nic); EC(50)=52 microM). I(Nic) was also blocked by atropine (EC(50)=1.7 microM) and hexamethonium (EC(50)=3.6 microM). 5-Hydroxytryptamine (5-HT) also inhibited I(ACh) in a concentration-dependent manner (EC(50)=180 microM) in the experiments carried out in the presence of a 5-HT(3) receptor antagonist. 5-HT had a similar inhibitory effect after the desensitization of 5-HT(3) receptors or in neurons with relative small 5-HT(3)-mediated currents. The inhibitory actions of hexamethonium, atropine, and 5-HT on I(ACh) were voltage-dependent. Thus, inhibition was significantly smaller for outward currents (recorded at +40 mV) than for inward currents (recorded at -60 mV). Our observations indicate that the I(ACh) of submucosal neurons are mediated by activation of nicotinic channels, which are blocked by atropine, 5-HT, and hexamethonium. The possibility that one of the 5-HT roles in the gastrointestinal tract might be to directly modulate nicotinic channels is discussed.

Acetylcholine↗
PubMed2000

Changes in intracellular Ca2+ by activation of P2 receptors in submucosal neurons in short-term cultures.

Electrophysiological and Ca2+ microfluorimetric techniques were used to characterize the pharmacological profile of the P2 receptors expressed in submucosal neurons and the changes in intracellular Ca2+ associated with activation of these receptors. ATP caused a fast and slow membrane depolarizations during intracellular recordings. ATP induced a rapid inward current during whole-cell experiments. Receptors mediating the inward current and fast depolarization have the same pharmacological profile and these ATP responses were more sensitive to pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid than Basilen BlueE-3G, and potentiated by suramin. The slow depolarization was not blocked by these P2 receptor antagonists, pertussis toxin, or KT5720 (protein kinase A inhibitor). N-ethylmaleimide or protein kinase C inhibitors (staurosporine and calphostin) blocked this depolarization. ATP induced complex multi-phasic Ca2+ transients in most neurons, classified as fast, slow, or mixed fast/slow responses. In conclusion, the fast and slow Ca2+ responses were mediated by respective activation of P2X and P2Y receptors and were associated with fast and slow depolarizations, respectively.

Adenosine Triphosphate↗
PubMed2000

Interferon-alpha inhibits long-term potentiation and unmasks a long-term depression in the rat hippocampus.

Interferons (IFN) appear to have various neuromodulatory actions. Here, we characterized the actions of IFN-alpha on the electrophysiological properties of CA1 hippocampal neurons using intracellular recordings. Superfusion of this cytokine did not alter the resting membrane potential, cell input resistance, action potentials, nor GABA-mediated fast synaptic potentials. IFN-alpha inhibited glutamate-mediated excitatory postsynaptic potentials (gEPSPs) and reversed or prevented long-term potentiation (LTP) induced by high-frequency tetanic stimulation. IFN-alpha reduced gEPSP amplitude far below its control value. Only a short-term potentiation (STP) was observed when either IFN-alpha or D-2-amino-5-phosphonovalerato (APV; NMDA receptor antagonist) were present during tetanic stimulation. After this STP in presence of APV, IFN-alpha had no effect on gEPSPs. APV had no effect on LTP when applied after tetanic stimulation and did also not prevent IFN-alpha effect on LTP. Genistein (a tyrosine kinase inhibitor) or heat inactivation prevented IFN-alpha effects. IFN-alpha also decreased the depolarization induced by local application of glutamate but did not modify those induced by NMDA. Similarly, IFN-alpha reversed the potentiation (induced by tetanic stimulation) of glutamate-induced depolarizations. IFN-alpha did not affect long-term depression (LTD) induced by low-frequency tetanic stimulation. In conclusion, IFN-alpha-induced inhibition of LTP is, at least in part, mediated by a postsynaptic effect, by tyrosine kinase activity, and by non-NMDA glutamate receptors. Inhibition of LTP by IFN-alpha unmasks LTD which is induced by the same high-frequency tetanic stimulation.

2-Amino-5-phosphonovalerate↗
PubMed2000

ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices.

It has been proposed that extracellular ATP inhibits synaptic release of glutamate from hippocampal CA1 synapses after its catabolism to adenosine. We investigated the possibility that at least part of this effect is mediated by ATP itself acting on P2Y receptors. ATP and various analogs decreased the amplitude and duration of glutamate-mediated excitatory postsynaptic potentials in all tested neurons. This effect was reversible and concentration-dependent and had the following rank order of agonist potency: AMP = ATP = adenosine-5'-O-(3-thio)triphosphate > adenosine = ADP. alpha,beta-Methylene ATP, beta,gamma-methylene ATP, 2-methylthioadenosine 5'-triphosphate, GTP, and UTP induced only a partial response. The depolarization induced by exogenous glutamate was not affected by ATP, indicating that this nucleotide acts presynaptically to inhibit glutamate-mediated excitatory postsynaptic potentials. Neither inhibition of ectonucleotidase activity with alpha,beta-methylene ADP, suramin, or pyridaxalphosphate-6-azophenyl-2',4'-disulfonic acid 4-sodium nor removal of extracellular adenosine (with adenosine deaminase) altered ATP effects. 8-Cyclopentyltheophylline competitively inhibited ATP effects, whereas P2 receptor antagonists (pyridaxalphosphate-6-azophenyl-2',4'-disulfonic acid 4-sodium, suramin, and reactive blue 2) were ineffective. ATP effects were by far more sensitive to pertussis toxin (PTX) than those of adenosine. After PTX, adenosine-5'-O-(3-thio)triphosphate induced only a partial response, and ATP concentration-response curve was biphasic. The second phase of this curve was blocked by adenosine deaminase, implying that it is mediated by adenosine as a result of ATP catabolism. Under control conditions, however, catabolism of ATP is not required to explain its actions. In conclusion, ATP inhibits synaptic release of glutamate by direct activation of P2Y receptors that are PTX- and 8-cyclopentyltheophylline-sensitive.

Adenosine Triphosphate↗
PubMed1999

Slow wave and spike action potentials recorded in cell cultures from the muscularis externa of the guinea pig small intestine.

Intracellular recordings were obtained to investigate whether slow wave and spike type action potentials are present in cell cultures of the muscularis externa from the guinea pig small intestine. The muscularis externa of the small intestine was dissociated by using specific purified enzymes and gentle mechanical dissociation. Cells were plated on cover slips and maintained in culture for up to 4 weeks. Dissociated cells obtained in this way reorganized themselves in a few days to form small cell clumps showing spontaneous movements. Intracellular recordings of these clumps displayed both spike and slow wave type action potentials. Spikes were observed on top of some slow waves and were abolished by the addition of nifedipine or the removal of extracellular calcium. Slow waves, however, were nifedipine insensitive and temperature sensitive, and were abolished by octanol (a gap junction blocker) and forskolin (an adenyl cyclase activator). Slow waves were never observed in small clumps (<50 microm), suggesting that a critical mass of cells might be required for their generation. These observations demonstrated for the first time the presence of nifedipine-insensitive slow waves in cell cultures of the muscularis externa from the guinea pig small intestine. Cell cultures allow rigorous control of the immediate environment for the cells and this should facilitate future studies on the molecular and cellular mechanisms responsible for the slow waves in the gastrointestinal tract.

Action Potentials↗
PubMed1998

Functional interactions between nicotinic and P2X channels in short-term cultures of guinea-pig submucosal neurons.

1. Functional interactions between nicotinic and P2X receptors in submucosal neurons were investigated. Whole-cell currents induced by ACh (IACh) and ATP (IATP) were blocked by hexamethonium and PPADS), respectively. Currents induced by simultaneous application of the two transmitters (IACh+ATP) were only as large as the current induced by the most effective of these substances. This current occlusion indicates that activation of nicotinic and P2X channels is not independent. 2. Kinetic parameters of IACh+ATP indicate that they are carried through channels activated by either substance. In agreement with this interpretation, both IACh and IATP amplitudes were decreased when ATP and ACh were applied simultaneously, whereas no cross-desensitization was observed when nicotinic and P2X receptors were desensitized individually. 3. Current occlusion was observed at membrane potentials of -60 and +10 mV, when IACh and IATP were inward. However, when these currents were outward (at +40 mV), current occlusion was not observed. Current occlusion was still observed at +40 mV in experiments in which the reversal potential of these currents had been adjusted to more positive values. 4. Current occlusion occurred as soon as currents were detected (< 5 ms), was still present in the absence of Ca2+, Na+ or Mg2+, and after adding staurosporine, genistein, K-252a, or N-ethylmaleimide to the pipette solution. Similar observations were noted after substituting alpha, beta-methylene ATP for ATP, or GTP for GTP-gamma-S in the pipette and in experiments carried out at 36, 23 and 9 C. 5. We propose that nicotinic and P2X channels are in functional clusters of at least two, and that the influx of ions through one activates (through allosteric interactions) a mechanism that inhibits the other channel.

Acetylcholine↗
PubMed1996

Melatonin modulates cholinergic transmission by blocking nicotinic channels in the guinea-pig submucous plexus.

Melatonin, a hormone produced and released by the pineal gland is also synthesized by cells of the gastrointestinal wall, where it might be a local regulator of gut functions. In this study, we investigated the possible role of melatonin as a modulator of the enteric nervous system. Intracellular recordings were made in neurons of the submucosal plexus from the guinea-pig ileum to measure the melatonin effects on their electrophysiological properties. Melatonin did not alter the membrane potential, the membrane resistance and the noradrenergic inhibitory postsynaptic potentials. However, melatonin (30-3000 microM) reversibly decreased the amplitude of nicotinic excitatory postynaptic potentials (EPSPs) in a concentration-dependent manner (IC50 = 247 microM). These actions of melatonin were not modified by the presence of idazoxan and atropine indicating that they are not mediated by endogenous release of acetylcholine, noradrenaline, or by direct activation of alpha 2-adrenoceptors or muscarinic receptors. The superfusion of melatonin also blocked the nicotinic depolarizations induced by locally applied acetylcholine, indicating that at least part of its effects are postsynaptic. In voltage-clamp experiments, using the whole-cell configuration, melatonin also inhibited the nicotinic inward currents induced by acetylcholine (IACh) in a concentration-dependent manner (IC50 = 257 microM). Melatonin decreased the maximal IACh but did not affect the potency of acetylcholine to induce this current, indicating a noncompetitive antagonism. This effect was voltage-dependent. Our observations indicate that melatonin inhibits the fast EPSPs by directly and specifically blocking the nicotinic channels. The relative high concentrations of melatonin required to produce such an effect rules this out as one of its humoral actions. Such an effect, however, might be of physiological significance close to the cells that release melatonin in the gastrointestinal wall or in other organs.

Acetylcholine↗
PubMed1996

P2x-purinoceptors of myenteric neurones from the guinea-pig ileum and their unusual pharmacological properties.

1. Whole-cell and outside-out patch clamp recordings were used to characterize the physiological and pharmacological properties of the P2x-purinoceptors of myenteric neurones from the guinea-pig ileum. 2. Adenosine 5'-triphosphate (ATP) and analogues (1-3000 microM) evoked a rapid inward current in > 90% of all recorded neurones. The reversal potential of this current was dependent on the extracellular sodium concentration, at +14 +/- 1.9, 0 +/- 1.6 and -12 +/- 1 mV for 166, 83 and 42 mM of sodium, respectively. The fast activation and inactivation of this current occurred even when guanosine 5'-triphosphate (GTP) was omitted from the pipette solution or substituted with an equimolar concentration of guanosine 5'-o-[2-thiotriphosphate] (GTP-gamma-S). Single channel currents were observed when these outside-out membrane patches were exposed to ATP (10-30 microM). These channels have a unitary conductance of about 17 picosiemens. 3. The rank-order of potency of the agonists used to induce the whole-cell currents was: ATP-gamma-S = ATP = 2-methylthio-ATP (2-Me-S-ATP) > > alpha, beta-methylene ATP = beta, gamma-methylene ATP; adenosine and uridine 5'-triphosphate (UTP) (up to 1 mM) were inactive. 4. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1-30 microM) antagonized the effects of ATP (1 mM) with an IC50 of 4 microM. alpha, beta-Methylene ATP (100 microM) did not affect the ATP (30 microM)-induced current. Cibacron Blue 3GA increased the ATP activated cationic current whereas Basilen Blue E-3G had a very weak antagonistic effect (IC50 > or = 3 mM). Suramin potentiated the currents induced by ATP through a mechanism that was independent of its inhibitory effect on ectonucleotidase activity, as suramin also potentiated the effect of alpha, beta-methylene ATP (an ATP analogue that is resistant to nucleotidases). 5. In conclusion, the myenteric P2x-purinoceptor shares some properties with other purinoceptors in particular with the P2x4- and P2x6-purinoceptors. This receptor has also some unusual pharmacological properties suggesting that myenteric neurones express a novel subtype of P2x-purinoceptors. The properties of this receptor, however, might be a result of the combination of two or more of the homomeric purinoceptors so far characterized.

Adenosine Triphosphate↗
PubMed1996

Cellular mechanisms underlying adenosine actions on cholinergic transmission in enteric neurons.

Whole cell recordings were used to investigate the effects of adenosine and several of its analogues on voltage-activated calcium currents (VACC) of myenteric and submucosal neurons. Electrophysiological and pharmacological properties of the soma VACC recorded in myenteric neurons indicate that they are carried through N-type calcium channels, similar to those of the submucosal neurons and to those of the calcium conductance that mediates acetylcholine release at the submucosal ganglia. Adenosinergic compounds inhibited, in a concentration-response and in a voltage-dependent manner, VACC in neurons from both enteric plexuses. The pharmacological profile of the receptors that mediate this effect was similar to that of the receptors involved in presynaptic inhibition in enteric neurons and likely of the A1 subtype. The effects of 2-chloroadenosine (CADO) on VACC were prevented by pretreatment with pertussis toxin (PTX), became irreversible with guanosine 5'-O-(3-thiotriphosphate) (inside the pipette), and were abolished with N-ethylmaleimide (NEM; known to uncouple receptors from G protein complexes). Intracellular recordings were used to further evaluate presynaptic effects of adenosine at the submucosal plexus. Adenosinergic compounds reduced the amplitude of fast excitatory postsynaptic potentials (EPSPs) by acting at nerve terminals. This effect was insensitive to PTX and staurosporine (a protein kinase inhibitor) but was abolished by NEM. CADO effects on EPSPs were not reversed by increasing the extracellular calcium concentration. In conclusion, activation of A1 adenosine receptors inhibits VACC via PTX-sensitive G proteins in myenteric and submucosal neurons. Reduction of cholinergic transmission also involves A1 adenosine receptors and appears to involve the activation of PTX-insensitive G proteins.

2-Chloroadenosine↗
PubMed1995

ATP inhibits the synaptic release of acetylcholine in submucosal neurons.

Previously, we have shown that adenosine inhibits release of acetylcholine (ACh) by acting at A1 presynaptic receptors in guinea pig submucosal synapses. In this study, intracellular recordings were made to investigate the actions of ATP and some analogs on the synaptic release of ACh. Superfusion of these substances decreased the amplitude and duration of electrically induced fast excitatory postsynaptic potentials (EP-SPs) in about 90% of the tested neurons. ATP (0.1-30 microM) effects were concentration dependent with an EC50 of 1.4 microM. ADP, AMP and ATP-gamma-S mimicked ATP inhibitory effects and were equally potent and efficacious. beta,gamma-Methylene-ATP seemed to act as a partial agonist, causing less than 50% of the inhibition obtained with ATP. 2-Methyl-thio-ATP was only active at the highest concentration tested whereas alpha,beta-methylene-ATP and UTP were inactive (0.3-30 microM). ATP-gamma-S did not alter depolarizations induced by exogenous application of ACh, indicating that ATP analogs inhibit EPSPs by acting at a presynaptic site. Although the EC50 values were similar for ATP and adenosine, the maximum responses (76 +/- 4.5% and 40 +/- 1.6%) were different. Adenosine deaminase (which inactivates adenosine) and alpha,beta-methylene-ADP (an ecto-5'-nucleotidase inhibitor) did not alter ATP-induced inhibition of these EPSPs. Inhibition of EPSPs by 30 microM adenosine (maximal concentration) and 1 microM ATP (submaximal concentration) were additive. Suramin or reactive blue 2 (30 microM), antagonists of ATP actions in several tissues, did not modify the effects of ATP on the fast EPSPs. 8-Cyclopentyltheophylline inhibited, in a competitive manner, these ATP inhibitory effects. In conclusion, ATP inhibits synaptic release of ACh by acting at receptors similar to those previously identified as P3-purinoceptors.

Acetylcholine↗
PubMed1994

Interactions between inhibitory and excitatory modulatory signals in single submucosal neurons.

Intracellular recordings were made in submucosal neurons from the guinea pig ileum to study the actions of norepinephrine and somatostatin on slow depolarizations induced by 2-chloroadenosine (CADO) and substance P. Local application (by pressure) of CADO and substance P induced a slow depolarization that occurred concomitantly with an increase in input membrane resistance. Norepinephrine, UK-14304 (alpha 2-adrenoceptor agonist), and somatostatin blocked the excitatory responses induced by CADO in a concentration-dependent manner. The alpha 2-adrenoceptor antagonists idazoxan and yohimbine antagonized these inhibitory effects of UK-14304 and norepinephrine. UK-14304 also decreased depolarizations induced by forskolin, but not those induced by the adenosine 3',5'-cyclic monophosphate analogue 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate. Slow depolarizations induced by substance P were blocked neither by UK-14304 nor by somatostatin. It was previously shown that staurosporine (an inhibitor of various protein kinases) and KT-5720 (an inhibitor of protein kinase A) inhibited slow depolarizations induced by CADO. Here, substance P depolarizations were inhibited by staurosporine and calphostin C (a blocker of protein kinase C) but not by KT-5720. In conclusion, activation of alpha 2-adrenoceptors and somatostatin receptors selectively blocks excitatory responses induced by CADO, most likely by inhibition of adenylyl cyclase and via pertussis toxin-sensitive G proteins. Slow depolarizations induced by substance P are independent of adenylyl cyclase activation and involve activation of protein kinase C.

2-Chloroadenosine↗
PubMed1994

ATP closes a potassium and opens a cationic conductance through different receptors in neurons of guinea pig submucous plexus.

Intracellular recordings were made to study the actions of ATP and related nucleotides on neurons from the guinea pig submucous plexus. Local application of ATP, by pressure, induced a depolarization in most AH-type neurons, which had a latency of several milliseconds, lasted for about 5 sec, appeared to reverse at about +4 mV and occurred concomitantly with a reduction in input resistance. Pressure application of ATP also depolarized the S-type neurons. In most of these cells the depolarization had two phases: the first component resembled the depolarization observed in AH cells and the second component was much slower in onset and was longer lasting (30-90 sec). The slower component was associated with an increase in input resistance, reversed polarity near the potassium equilibrium potential and was observed in isolation in 30% of S neurons. Superfusion of ATP or other analogs (0.03-10 microns) induced a slow depolarization in most of S neurons with the following rank order of potency: 2-methylthio-ATP > ATP > adenosine-5'-o-3-thiotriphosphate = ADP; alpha, beta-methylene ATP and beta, gamma-methylene ATP were inactive (10-100 microM). When whole-cell recordings were used, fast superfusion with ATP or other analogs (3-1000 microM) evoked, at negative membrane potentials, a rapidly desensitizing inward current. This current reversed polarity at about 0 mV and was much reduced in low extracellular sodium concentration. The rank order of potency of the used agonists was: ATP = adenosine-5'-o-3-thiotriphosphate = 2-methylthio-ATP > > alpha,beta-methylene ATP = beta,gamma-methylene ATP; adenosine, AMP or ADP (1 mM) were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Suramin increases the efficacy of ATP to activate an inward current in myenteric neurons from guinea-pig ileum.

Previous reports have indicated that suramin antagonizes, in a competitive manner, the actions of adenosine 5'-triphosphate (ATP) mediated by P2 purinoceptors. In neurons from the myenteric plexus, however, suramin has different effects on an ATP-activated conductance. During whole-cell recordings, ATP (3-1000 microM) evoked a rapidly desensitizing inward current in a concentration-dependent manner. The amplitude of the ATP-activated current was increased, in a reversible manner, when suramin was applied previous to or during ATP stimulation. This effect was increased by raising the suramin concentration. Higher concentrations of suramin were required for higher concentrations of ATP; the EC50 values of suramin were 5 +/- 1.1 microM and 143 +/- 48 nM when ATP concentrations of 30 and 10 microM were used. No change in the holding current was observed with suramin alone. These observations suggest that a different subtype of P2 purinoceptors could be expressed in the myenteric neurons.

Adenosine Triphosphate↗
PubMed1993

Adenosine reduces the potassium conductance of guinea pig submucosal plexus neurons by activating protein kinase A.

Intracellular recordings were made from S neurons of the submucosal plexus isolated from the guinea pig ileum. Adenosine or its analog 2-chloroadenosine (CADO) depolarized about 80% of neurons; previous work has shown that this results from activation of an A2 receptor. The depolarization was associated with an increase in membrane input resistance, became smaller with membrane hyperpolarization, reversed polarity at the potassium equilibrium potential and was mimicked and occluded by calcium-free solutions or by cadmium, suggesting that it is due to a reduction in a calcium-dependent potassium conductance. Both forskolin (though not 1,9-dideoxyforskolin) and phorbol 12,13-dibutyrate (PDBu) mimicked and occluded the action of CADO. Staurosporine (a nonspecific inhibitor of protein kinases) blocked the depolarization induced by the phorbol ester within 5 min, and blocked the effects of forskolin and CADO in 15-35 min. The depolarization caused by CADO was inhibited by the specific inhibitor of protein kinase A KT5720 [(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexylester-8-methyl-2,3,9,10-tet rahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]c ycloocta[cd e]-trin-den-1-one], whereas this inhibitor did not affect the depolarization induced by PDBu. The results are consistent with the control of this potassium conductance by protein kinase C, protein kinase A and intracellular calcium, and they indicate that adenosine reduces the conductance by activating protein kinase A.

2-Chloroadenosine↗
PubMed1993

New transmitters and new targets in the autonomic nervous system.

Several recent findings have made research into the autonomic nervous system even more exciting, such as the revelation that nitric oxide is a major neurotransmitter, the delineation of the physiological roles for purines and vasoactive intestinal peptide, and the discovery that the interstitial cells of Cajal are major target cells for enteric innervation. Nitric oxide is probably the major neurotransmitter evoking inhibitory junction potentials in smooth muscle. ATP is a mediator of non-adrenergic non-cholinergic enteric innervation, as well as being a fast neurotransmitter in peripheral and autonomic neuro-neuronal synapses. The interactions between enteric nerves and both immune cells and interstitial cells of Cajal (as pacemaker cells of gut smooth muscle) are forcing a rethink of many aspects of gut physiology.

Animals↗
PubMed1992

Ouabain-induced excitation of colonic smooth muscle due to block of K+ conductance by intracellular Na+ ions.

The mechanism by which ouabain causes excitation of canine colonic circular smooth muscle was investigated. Ouabain-induced depolarization and increase in contractility were related to the concentration of extracellular sodium and prevented by complete substitution of sodium ions with N-methyl-D-glucamine or lithium ions. Absence of external sodium ions did not prevent the depolarization and increase in contractility induced by tetraethylammonium. Exposure of the muscle strips to sodium-free solutions produced a transient hyperpolarization and decrease in the input membrane resistance consistent with the hypothesis that intracellular sodium blocks potassium conductance. The relationship between the membrane potential and the extracellular potassium concentration indicated that the resting membrane potential is mainly determined by the membrane potassium conductance. Our data suggest the following mechanism of action for ouabain: (a) ouabain blocks Na+/K+ pump thereby increasing the intracellular sodium concentration; (b) increase in intracellular sodium inhibits membrane potassium conductance, which depolarizes the membrane and prolongs the slow wave plateau, resulting in an increase of the force of contraction. The direct contribution of the sodium pump to the resting membrane potential, if any, can only be minor (< 6 mV).

Animals↗
PubMed1989

Quinidine and quinine effects on the slow wave activity of colonic circular muscle.

The slow wave plateau phase has an important role in the regulation of contractile activity in the canine colon. Quinidine (EC50 approximately 5 microM) and quinine (EC50 approximately 13 microM) inhibited in a concentration dependent manner the plateau phase. Quinidine and quinine decreased the plateau amplitude, and increased the plateau potential; whereas, they did not affect the upstroke amplitude, and the average rate of rise of the slow waves. Their specific effect on the slow wave plateau suggests that the plateau phase depolarization is mediated by a quinidine- and quinine-sensitive inward current. Quinidine and quinine will be useful experimental tools to further characterize the ionic conductances responsible for the plateau depolarization.

Animals↗