Biomedical subjects

F D Supan

Publications and source records attributed to F D Supan.

4 recordsLinked to original sources

PubMed1995

Halothane and isoflurane decrease the open state probability of K+ channels in dog cerebral arterial muscle cells.

BACKGROUND: Both halothane and isoflurane evoke cerebral vasodilation. One of the potential mechanisms for arterial vasodilation is enhanced K+ efflux resulting from an increased opening frequency of membrane K+ channels. The current study was designed to determine the effects of volatile anesthetics on K+ channel current in single vascular smooth muscle cells isolated from dog cerebral arteries. METHODS: Patch clamp recording techniques were used to investigate the effects of volatile anesthetics on macroscopic and microscopic K+ channel currents. RESULTS: In the whole-cell patch-clamp mode, in cells dialyzed with pipette solution containing 2.5 mM EGTA and 1.8 mM CaCl2, depolarizing pulses from -60 to +60 mV elicited an outward K+ current that was blocked 65 +/- 5% by 3 mM tetraethylammonium (TEA). Halothane (0.4 and 0.9 mM) depressed the amplitude of this current by 18 +/- 4% and 34 +/- 6%, respectively. When 10 mM EGTA was used in the pipette solution to strongly buffer intracellular free Ca2+, an outward K+ current insensitive to 3 mM TEA was elicited. This K+ current, which was reduced 51 +/- 4% by 1 mM 4-aminopyridine, was also depressed by 17 +/- 5% and 29 +/- 7% with application of 0.4 and 0.9 mM halothane, respectively. In cell-attached patches using 145 mM KCl in the pipette solution and 5.2 mM KCl in the bath, the unitary conductance of the predominant channel type detected was 99 pS. External application of TEA (0.1 to 3 mM) reduced the unitary current amplitude of the 99 pS K+ channel in a concentration-dependent manner. The open state probability of this 99 pS K+ channel was increased by 1 microM Ca2+ ionophore (A23187). These findings indicate that the 99 pS channel measured in cell-attached patches was a TEA-sensitive, Ca(2+)-activated K+ channel. Halothane and isoflurane reversibly decreased the open state probability (NPo), mean open time, and frequency of opening of this 99 pS K+ channel without affecting single channel amplitude or the slope of the current-voltage relationship. CONCLUSIONS: Halothane and isoflurane suppress the activity of K+ channels in canine cerebral arterial cells. These results suggest that mechanisms other than K+ channel opening likely mediate volatile anesthetic-induced vasodilation.

Animals↗

PubMed1993

The effects of halothane and isoflurane on slowly inactivating sodium current in canine cardiac Purkinje cells.

The effects of halothane (0.45 and 0.9 mM, equivalent to 0.7 and 1.5 vol%, respectively) and isoflurane (0.56 and 1.23 mM, equivalent to 0.9 and 2.0 vol%) on slowly inactivating Na+ current were examined by whole-cell voltage-clamp techniques. This approach allows evaluation of the role of anesthetic inhibition of inward Na+ current on the action potentials of canine Purkinje fibers isolated from the false tendons. Cells were superfused with Tyrode's solution containing nifedipine and Ni2+ to block Ca2+ channel currents and internally dialyzed with Cs+ to block outward K+ currents. Veratridine (0.5 microM) was used throughout the experiments to enhance the slow Na+ current. Na+ current was elicited by depolarizing pulses from a holding potential of -100 mV to stepwise (10 mV increments) more positive membrane potentials and measured at 200 ms after initiation of the voltage pulse before, during, and after exposure to anesthetics. Slowly inactivating Na+ current showed threshold activation at -80 mV and peak activation around -55 to -40 mV. This current was abolished by 5 microM tetrodotoxin, showing the characteristic feature of Na+ channel current. Halothane and isoflurane depressed the amplitude of slowly inactivating Na+ current in a concentration-dependent manner and did not shift the current-voltage relationship for slow Na+ current activation. There was no significant difference between the sensitivities of slow Na+ current to halothane or isoflurane at equianesthetic concentrations. Inhibition of slow inward Na+ current may contribute to the marked decrease of action potential duration produced by volatile anesthetics in false tendon Purkinje fibers but does not account for the larger decreases of duration produced by isoflurane than halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1991

The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells.

The effects of halothane, enflurane, and isoflurane on voltage-dependent Ca2+ channel current (ICa) were compared in canine ventricular cells by the whole-cell voltage-clamp technique. ICa was elicited in each cell by progressively depolarizing pulses, from -80 or -40 mV to more positive membrane potentials. The peak amplitude and inactivation rate of the inward current were analyzed before, during, and after the external application of equianesthetic concentrations (0.5, 1.0, and 2.0 MAC) of halothane, enflurane, or isoflurane. The concentrations of these agents in the Krebs' solution were as follows (percentage in the gas phase): halothane 0.36, 0.68, and 1.50%; isoflurane 0.50, 1.00, and 1.90%; and enflurane 0.66, 1.36, and 2.39%. Halothane, enflurane, and isoflurane rapidly reduced peak ICa amplitude at all voltages studied, resulting in a depression of the entire current-voltage relationship for ICa activation. This depression was concentration-dependent and completely reversible upon wash-out of the anesthetic agents. Quantitatively, the three anesthetic agents produced a similar inhibition of peak ICa at approximately equianesthetic concentrations. Inactivation of ICa during 200-ms depolarizing pulses was not affected by two lower concentrations of the anesthetic agents, but was accelerated by the highest concentration of enflurane used. These findings suggest that the negative inotropic and chronotropic actions of halothane, enflurane, and isoflurane on the ventricular myocardium are related, at least in part, to their inhibition of ICa at the sarcolemma. However, since all three anesthetic agents depressed ICa amplitude similarly, their quantitatively different effects on cardiac performance are due most likely to differences in actions at other cellular sites.

Animals↗

PubMed1991

The effects of volatile anesthetics on L- and T-type calcium channel currents in canine cardiac Purkinje cells.

The effects of halothane (0.45 and 0.9 mM, equivalent to 0.7 and 1.5%, respectively), isoflurane (0.54 and 1.23 mM, equivalent to 0.9 and 2.0%, respectively) and enflurane (0.65 and 1.48 mM, equivalent to 1.2 and 2.5%, respectively) on macroscopic L- and T-type Ca2+ channel currents were compared in single canine cardiac Purkinje cells using the whole-cell voltage-clamp technique. Cells were dialyzed with pipette solution containing CsCl and superfused with an external solution containing 10 mM BaCl2 and tetraethylammonium chloride. The long-lasting (L) and transient (T)-type Ca2+ channel currents were measured by depolarizing the membrane from different holding potentials (HPs). Voltage steps from an HP of either -80 or -70 mV elicited a low threshold, rapidly inactivating inward current at -40 to -30 mV, which maximally activated at -14 +/- 0.9 mV. This current was reduced by Ni2+ (100 microM) but not by nifedipine (1 microM), therefore resembling T-type Ca2+ channel current. In contrast, depolarizing steps from an HP of -40 mV elicited a sustained inward current that maximally activated at +4.1 +/- 0.8 mV and was nifedipine-sensitive, showing the characteristics of an L-type Ca2+ channel current. Halothane, isoflurane, and enflurane produced a concentration-dependent suppression of total Ca2+ channel current in every cell studied. Separation of Ca2+ channel types showed that both L- and T-type Ca2+ channel currents were depressed to a similar extent by anesthetic administration. These agents reduced peak L- and T-type current elicited at each pulse potential but did not shift the current-voltage (I-V) relationship for either T- or L-type current activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗