Disopyramide phosphate effects on slow and depressed fast responses

1986 ◽  
Vol 64 (4) ◽  
pp. 487-491 ◽  
Author(s):  
Otto F. Schanne ◽  
G. Bkaily ◽  
B. Dumais ◽  
L. Boutin
Keyword(s):  
Spontaneous Activity ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Fast Response ◽  
Membrane Depolarization ◽  
Neonatal Rat ◽  
Slow Response ◽  
Beating Rate ◽  
Rat Ventricle ◽  
Fast Responses

We studied the effects of disopyramide phosphate on explanted neonatal rat ventricle cells exhibiting depressed fast responses or naturally occurring slow response action potentials together with automatic activity. Disopyramide suppressed the spontaneous activity at a concentration of 2.5 μg/mL with a half-maximal value of 10 μg/mL. Before spontaneous activity was lost, there was an increase in beating rate possibly related to membrane depolarization. In depressed fast and slow response action potentials there was an increase in action potential duration (APD) which was consistently found both at the level of the plateau and at 90% repolarization. Comparison of the APD increase observed after disopyramide treatment and that after exposure to 20 mM tetraethylammonium suggested a block of a potassium conductance as a possible cause underlying the change in APD. The [Formula: see text] values of the depressed fast response decreased at constant membrane potential and this was attributed to the local anesthetic effect of the drug. In addition, we report two novel findings: (i) a decrease of [Formula: see text] of the slow response action potentials which may be secondary to membrane depolarization, and (ii) an increase in the duration of slow action potentials, possibly caused by inhibition of a potassium conductance.

scholarly journals Nervous Control of Movement in Annelids

1960 ◽  
Vol 37 (1) ◽  
pp. 46-56
Author(s):  
DONALD MELVIN WILSON
Keyword(s):  
Motor Neurons ◽  
Fast Response ◽  
Slow Response ◽  
Nervous Control ◽  
Chemical Stimuli ◽  
Nerve Muscle ◽  
Slow System ◽  
Fast Responses ◽  
Stimulation Of

1. Nerve muscle preparations of the segmental nerves and associated muscles have been made using a nereid polychaete, Neanthes brandti (Malmgren). 2. Two kinds of response, differing in threshold and latency, were found. The ‘fast’ response is large at the first shock and (at frequencies above 1/sec.) decreases thereafter. The ‘slow’ response is small but facilitates with repetition at frequencies above 10/sec. Facilitation reaches a maximum after 3 or 4 shocks. 3. Isolated parapodia show several distinct reflex movements to mechanical and chemical stimuli. These must involve motor neurons in the parapodial ganglion. 4. Stimulation of the segmental nerves of the leech, Hirudo, evokes facilitating muscle potentials resembling in most details those of the ‘slow‘ system in Neanthes. 5. The ‘fast’ and ‘slow’ responses are discussed in comparison with other invertebrate systems, especially those of arthropods. The ‘slow’ responses in annelids show less facilitation. The ‘fast’ responses of polychaetes fatigue quickly and are probably useful only in ‘startle’ responses.

scholarly journals Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal rat ventricle.

1993 ◽  
Vol 57 (9) ◽  
pp. 912-920 ◽  
Author(s):  
HIROYUKI ORITA ◽  
MANABU FUKASAWA ◽  
SHIGEKI HIROOKA ◽  
HIDEAKI UCHINO ◽  
KANA FUKUI ◽  
...  
Keyword(s):  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Neonatal Rat ◽  
Beating Rate ◽  
Rat Ventricle

Effects of Serotonin on Caudal Raphe Neurons: Activation of an Inwardly Rectifying Potassium Conductance

1997 ◽  
Vol 77 (3) ◽  
pp. 1349-1361 ◽  
Author(s):  
Douglas A. Bayliss ◽  
Yu-Wen Li ◽  
Edmund M. Talley
Keyword(s):  
Brain Stem ◽  
Rat Brain ◽  
Pertussis Toxin ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Neonatal Rat ◽  
Serotonergic Neurons ◽  
Inwardly Rectifying ◽  
Neonatal Rat Brain ◽  
Raphe Neurons

Bayliss, Douglas A., Yu-Wen Li, and Edmund M. Talley. Effects of serotonin on caudal raphe neurons: activation of an inwardly rectifying potassium conductance. J. Neurophysiol. 77: 1349–1361, 1997. We used whole cell current- and voltage-clamp recording in neonatal rat brain stem slices to characterize firing properties and effects of serotonin (5-HT) on neurons( n = 225) in raphe pallidus (RPa) and raphe obscurus (ROb). Of a sample of 51 Lucifer yellow-filled neurons recovered after immunohistochemical processing to detect tryptophan hydroxylase (TPH), 34 were found to be TPH immunoreactive (i.e., serotonergic). Serotonergic neurons had long-duration action potentials and fired spontaneously at low frequency (∼1 Hz) in a pattern that was often irregular; at higher firing frequencies the discharge became more regular. These neurons displayed spike frequency adaptation, with maximal steady-state firing rates of <4 Hz. The overwhelming majority of identified serotonergic neurons was hyperpolarized by bath-applied 5-HT (94%; n = 32 of 34); conversely, most cells in this sample that were hyperpolarized by 5-HT were serotonergic (78%; n = 32 of 41). TPH-immunonegative neurons were separated into two populations. One group had properties that were indistinguishable from those of serotonergic caudal raphe neurons. The other group was truly distinct; those neurons had more hyperpolarized resting membrane potentials, were not spontaneously active, had shorter-duration action potentials, and were depolarized by 5-HT. Caudal raphe neurons responded to 5-HT (1–5 μM) with membrane hyperpolarization in current clamp (−13.4 ± 1.1 mV, mean ± SE) or with outward current in voltage clamp (16.0 ± 1.4 pA). The current induced by 5-HT was inwardly rectifying and associated with an increase in peak conductance and was highly selective for K+. It was completely blocked by 0.2 mM Ba2+ but not by glibenclamide, an inhibitor of ATP-sensitive K+ channels. Effects of 5-HT were dose dependent, with an EC50 of 0.1–0.3 μM. The 5-HT1A agonist 8-OH-DPAT mimicked, and the 5-HT1A antagonists (+)WAY 100135 and NAN 190 blocked, effects of 5-HT. The 5-HT2A/C antagonist ketanserin did not inhibit the effects of 5-HT. Fewer 5-HT-responsive neurons were encountered in slices exposed acutely to pertussis toxin (∼13%) than in adjacent control slices not exposed to pertussis toxin (∼85%). In addition, in neurons recorded with pipettes containing GTPγS (0.1 mM), 5-HT induced an inwardly rectifying current that did not reverse on washing. In many cells recorded with GTPγS, a current developed in the absence of agonist that had properties identical to those of the 5-HT-sensitive current; when followed for extended periods, the agonist-independent GTPγS-induced conductance desensitized, returning toward control levels with a time constant of ∼18 min. Together these results indicate that serotonergic neurons of ROb and RPa are spontaneously active in a neonatal rat brain stem slice preparation and that hyperpolarization of those neurons by 5-HT1A receptor stimulation is due to pertussis toxin-sensitive G protein-mediated activation of an inwardly rectifying K+ conductance. In addition, we identified a group of nonserotonergic medullary raphe neurons that had distinct electrophysiological properties and that was depolarized by 5-HT.

Effects of K-channel blockers, calcium, and verapamil suggest different pacemaker mechanisms in cultured neonatal rat and embryonic chick ventricle cells

1989 ◽  
Vol 67 (7) ◽  
pp. 795-800 ◽  
Author(s):  
Otto F. Schanne ◽  
L. Boutin ◽  
J. Derosiers
Keyword(s):  
Cardiac Cells ◽  
Neonatal Rat ◽  
K Channel ◽  
Chronotropic Effect ◽  
Inward Current ◽  
Diastolic Depolarization ◽  
K Current ◽  
Beating Rate ◽  
Rat Ventricle ◽  
Diastolic Potential

We compared the determinants of spontaneous activity in explanted neonatal (2-day-old) rat ventricle cells and in reaggregates derived from 15-day-old chick embryos. We studied the beating rate with an optical recording method and the underlying electrical activity with glass microelectrodes using the K current blockers cesium (Cs) and tetraethylammonium, varied Ca concentrations, and the Ca antagonist verapamil. In the rat (i) Cs increased the beating rate that was mediated by an increase in the slope of the diastolic potential, (ii) Ca increased the beating rate dramatically at low and medium concentrations to decrease it again at 8 mM Cao.2This increase in the beating rate was mediated by an increase of the slope of the diastolic depolarization. (iii) The beating rate decreased with verapamil at concentrations between 0.5 and 2.0 μM. The effects of Cs and Ca suggest that an increase in net inward current (block of IK1) underlies the positive chronotropic effect of Cs and that the pacemaker mechanism is determined by a Ca inward current or an IT1 type current modulated by variations of Cai. In the chick reaggregates (i) Cs and tetraethylammonium decreased the beating rate that was mainly brought about by a decrease in the slope of diastolic depolarization. (ii) Ca increased the beating rate but to a lesser degree than in the rat and there was no decrease of the beating rate at higher concentrations. (iii) The increase in the beating rate was not mediated by an increase in the slope of the diastolic potential but mainly by a depolarization of the maximum diastolic potential. (iv) Verapamil inhibited electrogenesis before any change in the diastolic potential was evident. The negative chronotropic effect of Cs and tetraethylammonium is compatible with the notion that a voltage- and time-dependent K current was inhibited and that this current determines the pacemaker. Moreover, the Ca component of the pacemaker mechanism in explanted rat ventricle cells resembles either that of the sinoatrial node or represents triggered activity.Key words: pacemaker mechanism, cultured cardiac cells, K-channel blocker, calcium, verapamil.

Influence of streptomycin on spontaneous activity of clusters of cultured cardiac cells from neonatal rats

1980 ◽  
Vol 58 (4) ◽  
pp. 433-435 ◽  
Author(s):  
M. D. Payet ◽  
G. Bkaily ◽  
O. F. Schanne ◽  
E. Ruiz-Ceretti
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Maximum Rate ◽  
Cardiac Cells ◽  
Neonatal Rats ◽  
Slow Response ◽  
Diastolic Depolarization ◽  
Beating Rate ◽  
Maximum Rate Of Rise ◽  
Diastolic Potential

In clusters of trypsinized ventricle cells from neonatal rats which exhibit slow response action potentials, streptomycin in concentrations from 0.17 to 5.5 mM significantly inhibits the beating rate. Microelectrode experiments performed at a concentration of 5.5 mM revealed a reduction in the slope of diastolic depolarization from 149 to 53 mV/s whereas the maximum diastolic potential depolarized from −42.4 to −33.6 mV which entailed a decrease in overshoot and maximum rate of rise of the action potential. We conclude that the decrease of the slope of diastolic depolarization mainly determines the slowing of the beating rate and that streptomycin interferes with the pacemaker mechanism usually associated with the slow response.

Calcium-dependent potassium conductance in rat supraoptic nucleus neurosecretory neurons

1985 ◽  
Vol 54 (6) ◽  
pp. 1375-1382 ◽  
Author(s):  
C. W. Bourque ◽  
J. C. Randle ◽  
L. P. Renaud
Keyword(s):  
Time Constant ◽  
Action Potentials ◽  
Supraoptic Nucleus ◽  
Potassium Conductance ◽  
Reversal Potential ◽  
Input Resistance ◽  
Mean Amplitude ◽  
Progressive Increase ◽  
Calcium Dependent ◽  
Neurosecretory Neurons

Intracellular recordings of rat supraoptic nucleus neurons were obtained from perfused hypothalamic explants. Individual action potentials were followed by hyperpolarizing afterpotentials (HAPs) having a mean amplitude of -7.4 +/- 0.8 mV (SD). The decay of the HAP was approximated by a single exponential function having a mean time constant of 17.5 +/- 6.1 ms. This considerably exceeded the cell time constant of the same neurons (9.5 +/- 0.8 ms), thus indicating that the ionic conductance underlying the HAP persisted briefly after each spike. The HAP had a reversal potential of -85 mV and was unaffected by intracellular Cl- ionophoresis of during exposure to elevated extracellular concentrations of Mg2+. In contrast, the peak amplitude of the HAP was proportional to the extracellular Ca2+ concentration and could be reversibly eliminated by replacing Ca2+ with Co2+, Mn2+, or EGTA in the perfusion fluid. During depolarizing current pulses, evoked action potential trains demonstrated a progressive increase in interspike intervals associated with a potentiation of successive HAPs. This spike frequency adaptation was reversibly abolished by replacing Ca2+ with Co2+, Mn2+, or EGTA. Bursts of action potentials were followed by a more prolonged afterhyperpolarization (AHP) whose magnitude was proportional to the number of impulses elicited (greater than 20 Hz) during a burst. Current injection revealed that the AHP was associated with a 20-60% decrease in input resistance and showed little voltage dependence in the range of -70 to -120 mV. The reversal potential of the AHP shifted with the extracellular concentration of K+ [( K+]o) with a mean slope of -50 mV/log[K+]o.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Lamotrigine on the Ca2+-Sensing Cation Current in Cultured Hippocampal Neurons

2001 ◽  
Vol 86 (5) ◽  
pp. 2520-2526 ◽  
Author(s):  
Zhi-Gang Xiong ◽  
Xiang-Ping Chu ◽  
J. F. MacDonald
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Membrane Depolarization ◽  
Slow Inward Current ◽  
Calcium Sensing ◽  
Cation Current ◽  
Imaging Experiment ◽  
Intracellular Ca ◽  
Cultured Hippocampal Neurons

Concentrations of extracellular calcium ([Ca2+]e) in the CNS decrease substantially during seizure activity. We have demonstrated previously that decreases in [Ca2+]e activate a novel calcium-sensing nonselective cation (csNSC) channel in hippocampal neurons. Activation of csNSC channels is responsible for a sustained membrane depolarization and increased neuronal excitability. Our study has suggested that the csNSC channel is likely involved in generating and maintaining seizure activities. In the present study, the effects of anti-epileptic agent lamotrigine (LTG) on csNSC channels were studied in cultured mouse hippocampal neurons using patch-clamp techniques. At a holding potential of −60 mV, a slow inward current through csNSC channels was activated by a step reduction of [Ca2+]e from 1.5 to 0.2 mM. LTG decreased the amplitude of csNSC currents dose dependently with an IC50 of 171 ± 25.8 (SE) μM. The effect of LTG was independent of membrane potential. In the presence of 300 μM LTG, the amplitude of csNSC current was decreased by 31 ± 3% at −60 mV and 29 ± 2.9% at +40 mV ( P > 0.05). LTG depressed csNSC current without affecting the potency of Ca2+ block of the current (IC50 for Ca2+block of csNSC currents in the absence of LTG: 145 ± 18 μM; in the presence of 300 μM LTG: 136 ± 10 μM. n = 5, P > 0.05). In current-clamp recordings, activation of csNSC channel by reducing the [Ca2+]e caused a sustained membrane depolarization and an increase in the frequency of spontaneous firing of action potentials. LTG (300 μM) significantly inhibited csNSC channel-mediated membrane depolarization and the excitation of neurons. Fura-2 ratiometric Ca2+imaging experiment showed that LTG also inhibited the increase in intracellular Ca2+ concentration induced by csNSC channel activation. The effect of LTG on csNSC channels may partially contribute to its broad spectrum of anti-epileptic actions.

Membrane resistance increases when automaticity develops in explanted rat heart cells

1990 ◽  
Vol 258 (1) ◽  
pp. H145-H152 ◽  
Author(s):  
O. F. Schanne ◽  
M. Lefloch ◽  
B. Fermini ◽  
E. Ruiz-Petrich
Keyword(s):  
Spontaneous Activity ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Input Resistance ◽  
Membrane Resistance ◽  
Resting Potential ◽  
Heart Cells ◽  
Membrane Capacity ◽  
Rat Heart Cells ◽  
Specific Membrane

We compared the passive electrical properties of isolated ventricular myocytes (resting potential -65 mV, fast action potentials, and no spontaneous activity) with those of 2- to 7-day-old cultured ventricle cells from neonatal rats (resting potential -50 mV, slow action potentials, and presence of spontaneous activity). In myocytes the specific membrane capacity was 0.99 microF/cm2, and the specific membrane resistance increased from 2.46 k omega.cm2 at -65 mV to 7.30 k omega.cm2 at -30 mV. In clusters, the current-voltage relationships measured under current-clamp conditions showed anomalous rectification and the input resistance decreased from 1.05 to 0.48 M omega when external K+ concentration was increased from 6 to 100 mM. Using the model of a finite disk we determined the specific membrane resistance (12.9 k omega.cm2), the effective membrane capacity (17.8 microF/cm2), and the lumped resistivity of the disk interior (1,964 omega.cm). We conclude that 1) the voltage dependence of the specific membrane resistance cannot completely explain the membrane resistance increase that accompanies the appearance of spontaneous activity; 2) a decrease of the inwardly rectifying conductance (gk1) is mainly responsible for the increase in the specific membrane resistance and depolarization; and 3) approximately 41% of the inward-rectifying channels are electrically silent when spontaneous activity develops in explanted ventricle cells.

scholarly journals Action Potentials in Rhodnius Oocytes: Repolarization is Sensitive to Potassium Channel Blockers

1986 ◽  
Vol 126 (1) ◽  
pp. 119-132
Author(s):  
M. J. O'DONNELL
Keyword(s):  
Potassium Channel ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Channel Blockers ◽  
Calcium Dependent ◽  
Outward Rectification ◽  
Current Voltage ◽  
Potassium Channel Blockers ◽  
Potassium Conductances ◽  
Voltage Dependent

Depolarization of Rhodnius oocytes evokes action potentials (APs) whose rising phase is calcium-dependent. The ionic basis for the repolarizing (i.e. falling) phase of the AP was examined. Addition of potassium channel blockers (tetraethylammonium, tetrabutylammonium, 4-aminopyridine, atropine) to the bathing saline increased the duration and overshoot of APs. Intracellular injection of tetraethyl ammonium had similar effects. These results suggest that a voltage-dependent potassium conductance normally contributes to repolarization. Repolarization does not require a chloride influx, because substitution of impermeant anions for chloride did not increase AP duration. AP duration and overshoot actually decreased progressively when chloride levels were reduced. Current/voltage curves show inward and outward rectification, properties often associated with potassium conductances. Outward rectification was largely blocked by external tetraethylammonium. Possible functions of the rectifying properties of the oocyte membrane are discussed.

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