The class III antiarrhythmic agent E-4031 selectively blocks the inactivating inward-rectifying potassium current in rat anterior pituitary tumor cells (GH3/B6 cells)

  title={The class III antiarrhythmic agent E-4031 selectively blocks the inactivating inward-rectifying potassium current in rat anterior pituitary tumor cells (GH3/B6 cells)},
  author={Frank Weinsberg and Christiane K. Bauer and J{\"u}rgen R Schwarz},
  journal={Pfl{\"u}gers Archiv},
Abstract Hyperpolarization-elicited potassium currents in GH3/B6 cells bathed in high-potassium external solution were recorded to assess effects of the class III antiarrhythmic agent E-4031 on the inactivating inward-rectifying potassium current (IK,IR). E-4031 potently blocked IK,IR with an IC50 value of 10 nM. The complete block of IK,IR achieved with concentrations ≥ 1 μM revealed the presence of a non-inactivating outward-rectifying current which contributed to the membrane currents… 
On the mechanism of selective action of probucol on the inwardly rectifying potassium current in GH3 lactotrophs
Substantial evidence is provided that in addition to the presence of antioxidant activity, probucol is a selective blocker of IK(IR), and implies that Probucol‐mediated blockade of this current may affect membrane excitability and hormonal secretion in GH3 cells.
The erg inwardly rectifying K+ current and its modulation by thyrotrophin‐releasing hormone in giant clonal rat anterior pituitary cells
  • C. Bauer
  • Biology
    The Journal of physiology
  • 1998
The results demonstrate that the TRH‐induced reduction of IK,IR is able to mediate the resting potential depolarization, suggesting that the increase in the frequency of action potentials occurring during the second phase of the TRh response in GH cells should be sustained by IK‐IR inhibition.
Isolation of a Long-Lasting eag-Related Gene-Type K+ Current in MMQ Lactotrophs and Its Accommodating Role during Slow Firing and Prolactin Release
It is suggested that IERGS potently modulates both firing and prolactin release in lactotroph cells as well as other anti-arrhythmic drugs.
Inhibition of BK channels contributes to the second phase of the response to TRH in clonal rat anterior pituitary cells.
It is proposed that inhibition of erg and BK channels acts in concert to enhance the cell excitability during the second phase of the response to TRH.
Ceramide Inhibits the Inwardly Rectifying Potassium Current in GH3 Lactotrophs.
Ceramide can produce a depressant effect on I(K(IR), and the blockade of this current by ceramide may affect cell function.
Demonstration of an inwardly rectifying K+ current component modulated by thyrotropin-releasing hormone and caffeine in GH3 rat anterior pituitary cells
An inwardly rectifying K+ current and not an M-like outward current seems to be involved in TRH and caffeine modulation of electrical activity in GH3 cells.
A role for inwardly rectifying K+ channels in differentiation of NG108-15 neuroblastoma x glioma cells.
An important role of the K(ir) channels is suggested in determining the RMP and triggering morphological differentiation of the cell line.


Effect of the class III antiarrhythmic agent E-4031 on the ATP-sensitive potassium channel in rabbit ventricular myocytes.
It is concluded that the class III antiarrhythmic drug E-4031 blocks the ATP-sensitive potassium channel and that it does so from within the cytoplasm, with one-to-one channel binding stoichiometry.
Cellular electrophysiology of WAY-123,398, a new class III antiarrhythmic agent: specificity of IK block and lack of reverse use dependence in cat ventricular myocytes.
The results indicate that WAY-123,398 is an effective and specific class III agent devoid of class I activity, and suggest that it prolongs cardiac repolarisation by specifically blocking the delayed rectifier current (IK).
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents
The magnitude of IKr was small relative to fully activated IKs, and the two currents were of similar magnitude when measured during a relatively short pulse protocol at membrane potentials typical of the plateau phase of cardiac action potentials.
Lanthanum blocks a specific component of IK and screens membrane surface change in cardiac cells.
The whole cell voltage-clamp technique is used on isolated myocytes and it is shown that the current blocked by La3+ (greater than or equal to 1 microM) is IK.s.r.
Effects of the New Class III Antiarrhythmic Drug E‐4031 on Myocardial Contractility and Electrophysiological Parameters
The class III antiarrhythmic action of E-4O3I is due to a selective reduction of outward currents, and the current changes that underlie the AP-prolonging effect were studied.
Cloned human inward rectifier K+ channel as a target for class III methanesulfonanilides.
It is shown that hIRK, a member of the two-transmembrane-segment family of inward K+ rectifiers that the authors have cloned from human heart, is a target for dofetilide.
The inactivating K+ current in GH3 pituitary cells and its modification by chemical reagents.
Intracellular application of the disulphonic stilbene derivative, SITS, and the protein‐modifying reagent, N‐bromoacetamide (NBA), at concentrations of 0.2‐1 mM for several tens of minutes dramatically slowed the decay (inactivation) of K+ currents and caused coincident increases in the magnitude of outward IK(i).
An Inactivating Inward-rectifying K Current Present in Prolactin Cells from the Pituitary of Lactating Rats
This current is similar to the inward-rectifying K current previously characterized in clonal somatomammotrophic pituitary cells (GH3B6) and the variability of the rate of inactivation of this current in lactotrophs and its responsiveness to TRH is discussed.
Characterization of an M-like current modulated by thyrotropin- releasing hormone in normal rat lactotrophs
The mechanism underlying the TRH-induced increase in firing frequency was investigated using the perforated-patch variation of the whole-cell patch-clamp technique and TRH was found to inhibit a voltage-dependent, noninactivating K+ current that was similar to M-currents originally identified in neurons.