Journal of Pharmacology and Experimental Therapeutics
The intravenous anesthestic thiopental has been previously shown to increase the incidence of ven... more The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ram...
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991, 1991
In the present paper we examined the effect of the barbiturate thiopental on the anomalous rectif... more In the present paper we examined the effect of the barbiturate thiopental on the anomalous rectifying K'current (IK1) in frog atrial myocytes. Thiopental, over a clinically useful range, rapidly suppresses IK1 in a dosedependent manner. Both inward and outward ...
The Journal of pharmacology and experimental therapeutics, 1998
Although tricyclic antidepressant (TCA) blockade of cardiac Na+ channels is appreciated, actions ... more Although tricyclic antidepressant (TCA) blockade of cardiac Na+ channels is appreciated, actions on neuronal Na+ channels are less clear. Therefore, the effects of TCAs (amitriptyline, doxepin and desipramine) as well as trazdone and fluoxetine on voltage-gated Na+ current (INa) were examined in bovine adrenal chromaffin cells using the whole-cell patch-clamp method. Amitriptyline produced concentration-dependent depression of peak INa evoked from a holding potential of -80 mV with KD value of 20.2 microM and a Hill coefficient of 1.2. Although 20 microM amitriptyline induced no change in the rate or voltage dependence of INa activation, steady-state inactivation demonstrated a 15-mV hyperpolarizing shift. Similar results were observed for doxepin and desipramine. This shift in steady-state inactivation was associated with a slowed rate of recovery from the inactivated state. Contrasting results were observed with the atypical antidepressants: while 20 microM fluoxetine depressed pe...
The Journal of pharmacology and experimental therapeutics, 1993
The intravenous anesthestic thiopental has been previously shown to increase the incidence of ven... more The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ram...
The effects of the inhalational anesthetics halothane and isoflurane on voltage-gated ionic curre... more The effects of the inhalational anesthetics halothane and isoflurane on voltage-gated ionic currents in bovine adrenal chromaffin cells were examined using patch-clamp techniques. Halothane (1.5% atmospheres, 0.90 mM in solution) and isoflurane (2.5% atmospheres, 0.78 mM in solution) diminished the Ca(2+)-dependent K+ current (IK(Ca)) "hump" by 52 +/- 3% (n = 16 cells) and 40 +/- 4% (n = 6), respectively. These concentrations of halothane and isoflurane had virtually no effect on the rapid inward Na+ current and exerted only minor effects on outward K+ currents in the absence of external Ca2+. The effectiveness of halothane (0.90 mM) was reduced by increasing the external Ca2+ concentration ([Ca2+]o); IK(Ca) was decreased by 64 +/- 4% (n = 4) with 1 mM [Ca2+]o but by only 37 +/- 4% (n = 4) with 10 mM [Ca2+]o. Voltage-activated Ca2+ current (ICa), isolated by intracellular perfusion with Cs+ and tetraethylammonium in the presence of 15-30 microM external tetrodotoxin, was i...
The dihydropyridine, Bay K 8644, was applied in vitro to mouse phrenic nerve-diaphragm muscle pre... more The dihydropyridine, Bay K 8644, was applied in vitro to mouse phrenic nerve-diaphragm muscle preparations. The drug increased both spontaneous and evoked release of acetylcholine from the motor nerve terminal in a concentration- and time-dependent manner. The rise in miniature endplate potential frequency, however, was the result of an increased intraterminal mobilization of free calcium, rather than well-established activation of voltage-dependent calcium channels. This view is supported by the following observations: (1) an increase in frequency was apparent in Ca2+-free medium; (2) Bay K 8644 is known to require a moderate depolarization to affect Ca2+ channels, but no membrane depolarization was detected; and (3) exposure to low Ca2+ and high Mg2+ medium did not diminish the effect on miniature endplate potential frequency. In a medium containing low Ca2+ and high Mg2+, Bay K 8644 increased quantal content of the evoked endplate potentials to a greater degree and with a faster ...
The Journal of pharmacology and experimental therapeutics, 1991
Verapamil, Ca++ channel antagonist, has proven clinically useful in the reversal of multiple drug... more Verapamil, Ca++ channel antagonist, has proven clinically useful in the reversal of multiple drug resistance, which is a major detriment to chemotherapy. Recently, verapamil alone has been shown to diminish proliferation in a variety of neoplastic cell lines. Using the patch-clamp technique, the action of verapamil on voltage-gated K+ channels in two cell lines of human small-cell carcinoma of the lung, NCI-H146 and NCI-H82, was investigated. With inward Na+ current suppressed, virtually all control cells exhibited a slowly inactivating outward current that was insensitive to alterations in the external Ca++ concentration. Externally applied verapamil enhanced the rate and extent of outward K+ current (IK) inactivation. Verapamil at a concentration of 20 microM diminished peak IK, evoked by a test pulse to +60 mV from a holding potential of -80 mV, from 1.38 +/- 0.11 nA (mean +/- S.E.M., n = 29 cells) to 0.56 +/- 0.13 nA (n = 11) and caused IK to decay to less than 20% of the peak c...
... A phone interview also was conducted using a pre-written ques-tionnaire, to obtain relevant a... more ... A phone interview also was conducted using a pre-written ques-tionnaire, to obtain relevant additional history and current status of NPG and CIED. ... M ean f/u period (months), range In te rference ... Neuromodulation 2010; : 2010 International Neuromodulation Society ...
Journal of Pharmacology and Experimental Therapeutics
The intravenous anesthestic thiopental has been previously shown to increase the incidence of ven... more The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ram...
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991, 1991
In the present paper we examined the effect of the barbiturate thiopental on the anomalous rectif... more In the present paper we examined the effect of the barbiturate thiopental on the anomalous rectifying K'current (IK1) in frog atrial myocytes. Thiopental, over a clinically useful range, rapidly suppresses IK1 in a dosedependent manner. Both inward and outward ...
The Journal of pharmacology and experimental therapeutics, 1998
Although tricyclic antidepressant (TCA) blockade of cardiac Na+ channels is appreciated, actions ... more Although tricyclic antidepressant (TCA) blockade of cardiac Na+ channels is appreciated, actions on neuronal Na+ channels are less clear. Therefore, the effects of TCAs (amitriptyline, doxepin and desipramine) as well as trazdone and fluoxetine on voltage-gated Na+ current (INa) were examined in bovine adrenal chromaffin cells using the whole-cell patch-clamp method. Amitriptyline produced concentration-dependent depression of peak INa evoked from a holding potential of -80 mV with KD value of 20.2 microM and a Hill coefficient of 1.2. Although 20 microM amitriptyline induced no change in the rate or voltage dependence of INa activation, steady-state inactivation demonstrated a 15-mV hyperpolarizing shift. Similar results were observed for doxepin and desipramine. This shift in steady-state inactivation was associated with a slowed rate of recovery from the inactivated state. Contrasting results were observed with the atypical antidepressants: while 20 microM fluoxetine depressed pe...
The Journal of pharmacology and experimental therapeutics, 1993
The intravenous anesthestic thiopental has been previously shown to increase the incidence of ven... more The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ram...
The effects of the inhalational anesthetics halothane and isoflurane on voltage-gated ionic curre... more The effects of the inhalational anesthetics halothane and isoflurane on voltage-gated ionic currents in bovine adrenal chromaffin cells were examined using patch-clamp techniques. Halothane (1.5% atmospheres, 0.90 mM in solution) and isoflurane (2.5% atmospheres, 0.78 mM in solution) diminished the Ca(2+)-dependent K+ current (IK(Ca)) "hump" by 52 +/- 3% (n = 16 cells) and 40 +/- 4% (n = 6), respectively. These concentrations of halothane and isoflurane had virtually no effect on the rapid inward Na+ current and exerted only minor effects on outward K+ currents in the absence of external Ca2+. The effectiveness of halothane (0.90 mM) was reduced by increasing the external Ca2+ concentration ([Ca2+]o); IK(Ca) was decreased by 64 +/- 4% (n = 4) with 1 mM [Ca2+]o but by only 37 +/- 4% (n = 4) with 10 mM [Ca2+]o. Voltage-activated Ca2+ current (ICa), isolated by intracellular perfusion with Cs+ and tetraethylammonium in the presence of 15-30 microM external tetrodotoxin, was i...
The dihydropyridine, Bay K 8644, was applied in vitro to mouse phrenic nerve-diaphragm muscle pre... more The dihydropyridine, Bay K 8644, was applied in vitro to mouse phrenic nerve-diaphragm muscle preparations. The drug increased both spontaneous and evoked release of acetylcholine from the motor nerve terminal in a concentration- and time-dependent manner. The rise in miniature endplate potential frequency, however, was the result of an increased intraterminal mobilization of free calcium, rather than well-established activation of voltage-dependent calcium channels. This view is supported by the following observations: (1) an increase in frequency was apparent in Ca2+-free medium; (2) Bay K 8644 is known to require a moderate depolarization to affect Ca2+ channels, but no membrane depolarization was detected; and (3) exposure to low Ca2+ and high Mg2+ medium did not diminish the effect on miniature endplate potential frequency. In a medium containing low Ca2+ and high Mg2+, Bay K 8644 increased quantal content of the evoked endplate potentials to a greater degree and with a faster ...
The Journal of pharmacology and experimental therapeutics, 1991
Verapamil, Ca++ channel antagonist, has proven clinically useful in the reversal of multiple drug... more Verapamil, Ca++ channel antagonist, has proven clinically useful in the reversal of multiple drug resistance, which is a major detriment to chemotherapy. Recently, verapamil alone has been shown to diminish proliferation in a variety of neoplastic cell lines. Using the patch-clamp technique, the action of verapamil on voltage-gated K+ channels in two cell lines of human small-cell carcinoma of the lung, NCI-H146 and NCI-H82, was investigated. With inward Na+ current suppressed, virtually all control cells exhibited a slowly inactivating outward current that was insensitive to alterations in the external Ca++ concentration. Externally applied verapamil enhanced the rate and extent of outward K+ current (IK) inactivation. Verapamil at a concentration of 20 microM diminished peak IK, evoked by a test pulse to +60 mV from a holding potential of -80 mV, from 1.38 +/- 0.11 nA (mean +/- S.E.M., n = 29 cells) to 0.56 +/- 0.13 nA (n = 11) and caused IK to decay to less than 20% of the peak c...
... A phone interview also was conducted using a pre-written ques-tionnaire, to obtain relevant a... more ... A phone interview also was conducted using a pre-written ques-tionnaire, to obtain relevant additional history and current status of NPG and CIED. ... M ean f/u period (months), range In te rference ... Neuromodulation 2010; : 2010 International Neuromodulation Society ...
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