James Herrington

Bio: James Herrington is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Halothane & Voltage clamp. The author has an hindex of 6, co-authored 6 publications receiving 291 citations. Previous affiliations of James Herrington include Florida State University.

Halothane inhibits two components of calcium current in clonal (GH3) pituitary cells.

Abstract: The effect of halothane on isolated calcium (Ca2+) current of clonal (GH3) pituitary cells was investigated using standard whole-cell clamp techniques at room temperature. Halothane (0.1–5.0 mM) reversibly reduced both the low-threshold, transient [low-voltage-activated (LVA)] component and the high-threshold [high-voltage-activated (HVA)] component of Ca2+ current. Halothane had little effect on the voltage dependence of activation or inactivation of either component of Ca2+ current. Inhibition of the peak high-threshold Ca2+ current was half- maximal at about 0.8 mM halothane, with maximal inhibition (100%) occurring with 5 mM halothane. When measured at the end of a 190-msec command step, half-maximal reduction of high-threshold current occurred at less than 0.5 mM halothane. The low-threshold transient current was less sensitive to halothane, with half-maximal inhibition of peak transient current activated at -30 mV occurring at approximately 1.3 mM. The effect of halothane on the HVA current was apparently not mediated by changes in intracellular Ca2+ concentration. The ability of halothane to inhibit Ca2+ current was unaffected by either the inclusion of the rapid Ca2+ buffer 1,2-bis(2-aminophenoxy)ethane N,N,N′,N′-tetraacetic acid (BAPTA) in the recording pipette or exposure of the cell to 10 mM caffeine. To assess the selectivity of the effect of halothane, the actions of halothane on two components of voltage- activated potassium (K+) current observed in the absence of extracellular Ca2+ and on voltage-dependent sodium (Na+) current were also examined. Halothane had no effect on the voltage-dependent, inactivating K+ current of GH3 cells at concentrations up to 1.2 mM. In contrast, the non-inactivating K+ current, though less sensitive to halothane than either Ca2+ current, was reduced by about 40% by 1.2 mM halothane at +20 mV. Peak Na+ current was also blocked by halothane, but 50% block required around 2.6 mM halothane with little effect at 1.6 mM. Reduction of Na+ current was associated with a substantial negative shift in the steady-state inactivation curve. Although the results indicate that a number of voltage-dependent ionic currents are sensitive to halothane, both components of Ca2+ current exhibit a greater sensitivity to halothane than any of three other voltage- dependent currents in GH3 cells. These results show that GH3 cell Ca2+ currents are selectively inhibited by clinically appropriate concentrations of halothane and that the reduction of Ca2+ current can account for the inhibition by halothane of TRH- or KCl-induced prolactin secretion in GH3 cells.

Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells.

Abstract: 1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of...

The suppression of Ca(2+)‐ and voltage‐dependent outward K+ current during mAChR activation in rat adrenal chromaffin cells.

Abstract: 1. The mechanism by which muscarine, ionomycin or caffeine results in suppression of Ca(2+)- and voltage-dependent outward current in rat adrenal chromaffin cells was evaluated using both whole-cell voltage clamp and single channel recording. 2. The whole-cell current activated following the elevation of the cytosolic calcium concentration ([Ca2+]i) by muscarine inactivates with a time course comparable to that of single Ca(2+)- and voltage-dependent potassium (BK) channels. 3. The whole-cell inactivating current is pharmacologically similar to BK current. 4. The voltage dependence of inactivation and rate of recovery from inactivation are qualitatively similar for both whole-cell current and ensemble averages of single BK channels. Furthermore, changes in the rate of whole-cell current inactivation track expected changes in submembrane [Ca2+]. 5. The suppression of outward current can be accounted for solely by inactivation of BK channels and does not depend on the means by which [Ca2+]i is elevated. 6. Muscarinic acetylcholine receptor (mAChR) activation, changes in holding potential (-50 to -20 mV), and step depolarizations of different amplitude and duration were tested for their ability to elevate [Ca2+]i and thereby regulate the availability of BK current for activation. 7. Following muscarine-induced elevation of [Ca2+]i at holding potentials positive to -40 mV, the availability of BK current for activation was typically reduced by more than 50%. 8. Holding potentials in the range of -50 to -20 mV produced only slight alterations in the availability of BK current for activation. 9. Step depolarizations that cause maximal rates of Ca2+ influx (0 to +10 mV) must exceed 200 ms to reduce the availability of BK current by approximately 50%. 10. The results show that the muscarine-induced elevation of [Ca2+]i produces a profound reduction in the availability of BK channels for activation at membrane potentials likely to be physiologically meaningful. Although depolarization- induced Ca2+ influx can inactivate BK current, we propose that short duration depolarizations that occur during normal electrical activity will not significantly alter BK channel availability.

Multiple components of voltage-dependent potassium current in normal rat anterior pituitary cells.

Abstract: 1. Voltage-dependent K+ currents were studied in normal rat anterior pituitary cells using the patch-clamp technique. To obtain cultures enriched for lactotrophs, density gradient centrifugation wa...

The action of halothane on stimulus-secretion coupling in clonal (GH3) pituitary cells

Abstract: The effect of halothane on the physiological response to excitatory stimuli was assessed in clonal (GH3) pituitary cells. Halothane, at concentrations used to produce general anesthesia in animals (0.25-0.76 mM), inhibited thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) secretion. The sustained (extracellular calcium-dependent) phase of PRL secretion was 70 +/- 7% inhibited by the highest concentration of halothane tested (0.76 mM); 50% inhibition was produced by approximately 0.4 mM halothane. The early (largely inositol trisphosphate-mediated) phase of secretion was less sensitive to halothane; 0.76 mM halothane produced 18 +/- 2% inhibition of the early phase of secretion. Consistent with these observations, halothane inhibited (IC50 approximately 0.45 mM) the sustained phase of the TRH-induced rise in intracellular calcium ([Ca2+]i) to a greater extent than the initial [Ca2+]i peak. The sustained phase of the [Ca2+]i elevation was inhibited by 75 +/- 7% at the highest concentration of halothane tested (0.76 mM), whereas the peak [Ca2+]i was only inhibited by 14 +/- 5%, consistent with the observation that halothane did not inhibit TRH-stimulated inositide hydrolysis in these cells. Halothane (0.5 mM) did not inhibit phorbol ester- or ionomycin-induced PRL secretion, indicating that halothane has inconsequential effects on the secretory apparatus. Halothane (0.5 mM) also inhibited KCl-induced PRL secretion by 50-80% and the corresponding KCl-induced rise in [Ca2+]i by 68 +/- 6%. These data indicate that halothane inhibits secretagogue-stimulated PRL secretion by reducing the elevation of [Ca2+]i produced by calcium (Ca2+) influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular and cellular mechanisms of general anaesthesia

Abstract: General anaesthetics are much more selective than is usually appreciated and may act by binding to only a small number of targets in the central nervous system. At surgical concentrations their principal effects are on ligand-gated (rather than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Although the role of second messengers remains uncertain, it is now clear that anaesthetics act directly on proteins rather than on lipids.

Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels

Abstract: T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels because they can be activated by small depolarizations of the plasma membrane. In many neurons Ca2+ influx through L...

Low-Threshold Calcium Currents in Central Nervous System Neurons

Abstract: The low-threshold calcium current, or T current, has recently been demonstrated with voltage-clamp recordings in a variety of central nervous system (CNS) neurons. It is especially prominent in the soma and dendrites of neurons with robust calcium-dependent burst firing behaviors such as thalamic relay neurons and cerebellar Purkinje cells. Single-channel and macroscopic current behavior have been carefully investigated and kinetic schemes devised to completely describe the activation and inactivation processes. The kinetic properties of T current lead to activation of low-threshold spikes subsequent to transient membrane hyperpolarizations. Putative functional roles for T current include generation of low-threshold spikes that lead to burst firing, promotion of intrinsic oscillatory behavior, boosting of calcium entry, and synaptic potentiation.