A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel

doi:10.1016/0024-3205(92)90036-O

Life Sciences

Volume 51, Issue 24, 1992, Pages 1851-1856

https://doi.org/10.1016/0024-3205(92)90036-O Get rights and content

Abstract

We studied the blocking mechanism of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the ATP-sensitive K⁺ channel in the single ventricular myocytes using the inside-out patch clamp technique. The channel activity in response to 5-hydroxydecanoate varied with each membrane patch corresponding to the sensitivity to ATP. In this condition the exogenous application of cAMP or cAMP-dependent protein kinase (PKA) obviously recovered the ATP-sensitive K⁺ channel activity after channel deactivation. By contrast, in membrane patches exhibited low sensitivity to ATP, endogenous cAMP-dependent protein kinase inhibitor (PKI) depressed the channel activity and restored the inhibitory action of 5-hydroxydecanoate and ATP on the channel. These results suggest that PKA-PKI system is involved in the regulatory mechanism of gating activity of the ATP-sensitive K⁺ channel and the blocking action of 5-hydroxydecanoate and ATP appears to be exerted by potentiating the inhibitory action of PKI on the channel.

References (13)

C.D. Ashby et al.
J. Biol. Chem.
(1972)
I. Findlay
Pflügers Arch.
(1987)
T. Ohno-Shosaku et al.
Pflügers Arch.
(1987)
M. Takano et al.
Am. J. Physiol.
(1990)
A. Noma
Nature
(1983)
G-N. Tseng et al.
Pflügers Arch.
(1990)

There are more references available in the full text version of this article.

Cited by (14)

Mitochondrial K<inf>ATP</inf> channels in cell survival and death
2005, Journal of Molecular and Cellular Cardiology
Since the discovery of the mitochondrial ATP-sensitive potassium channel (mitoK_ATP) more than 13 years ago, it has been implicated in the processes of ischemic preconditioning (IPC), apoptosis and mitochondrial matrix swelling. Different approaches have been employed to characterize the pharmacological profile of the channel, and these studies strongly suggest that cellular protection well correlates with the opening of mitoK_ATP. However, there are many questions regarding mitoK_ATP that remain to be answered. These include the very existence of mitoK_ATP itself, its degree of importance in the process of IPC, its response to different pharmacological agents, and how its activation leads to the process of IPC and protection against cell death. Recent findings suggest that mitoK_ATP may be a complex of multiple mitochondrial proteins, including some which have been suggested to be components of the mitochondrial permeability transition pore. However, the identity of the pore-forming unit of the channel and the details of the interactions between these proteins remain unclear. In this review, we attempt to highlight the recent advances in the physiological role of mitoK_ATP and discuss the controversies and unanswered questions.
Modeling triggered cardiac activity: An analysis of the interactions between potassium blockade, rhythm pauses, and cellular coupling
1996, Mathematical Biosciences
It is known that under certain conditions, a combination of potassium channel blockade, sympathetic nervous activity, and pauses in sinus rhythm can increase the occurrence of cardiac arrhythmias. Although the arrhythmogenic interactions of these three factors are not completely understood, it is believed that the associated arrhythmias may be initiated by afterpotentials via a process that we refer to as propagated triggered activity. Using a two-cell computational model of ventricular action potential kinetics, we simulate nonuniform potassium blockade, sympathetic nervous activity, and pauses in sinus rhythm under conditions of hypokalemia. Under these conditions, the two-cell model suggests that (1) the arrhythmogenic interactions of potassium blockade and sympathetic nervous activity are highly dependent on heart rate; (2) triggered activity induced by potassium blockade would most likely occur during a pause in sinus rhythm; (3) during a sufficiently large pause in sinus rhythm, potassium blockade can induce triggered activity at normal levels of sympathetic activity; and (4) potassium blockade can increase the probability of triggered activity only if heart rate falls within a critical range. We also show that during pauses in sinus rhythm, two-cell triggering interactions between potassium blockade and sympathetic activity closely parallel the parametric displacement of the dynamic instability underlying the afterpotentials. Our results indicate that the behavior of the triggering mechanism studied here is consistent with that of pause-induced arrhythmias.
Glucagon induces Ca<sup>2+</sup>-dependent increase of reduced pyridine nucleotides in mouse pancreatic β-cells
1996, Biochimica et Biophysica Acta - Molecular Cell Research
Glucagon enhances the electrical activity of pancreatic β-cells. The mechanism of the glucagon-evoked enhancement of electrical activity was investigated in terms of glucose metabolism. ICR mice aged 6–12 weeks were used for experiments. Intracellular Ca²⁺ increased in parallel with the enhancement of electrical activity. The stimulating effect of glucagon on Ca²⁺ oscillation was suppressed by calmodulin-antagonists (Chlorpromazine, W-7, and trifluoperazine). To trace the glucagon-evoked change in glucose metabolism, the reduced pyridine nucleotide (NAD(P)H) fluorescence was monitored using the microfluorometry with the excitation of 360 nm and the emission of 465 nm in islet cell clusters mainly consisting of β-cells. In the presence of 2.5 mM Ca²⁺ glucagon (8.6 × 10⁻⁸M) increased the NAD(P)H fluorescence, while in the absence of Ca²⁺ the hormone had no effect on the fluorescence. Extracellular Ca²⁺ removal from the glucagon-containing perifusion solution decreased the fluorescence to the level which had been attained before glucagon was added. Chlorpromazine (10 μM) reversed the glucagon-induced increase of NAD(P)H fluorescence as well as removing Ca²⁺. W-7 (15 μM) and trifluoperazine (30 μM) also suppressed the glucagon-induced increase of NAD(P)H. These results suggest that Ca²⁺/calmodulin system is involved in the acceleration of glycogenolysis by glucagon in β-cells. On the basis of these observations, the mechanism of glucagon-induced enhancement of electrical activity and the relative ineffectiveness of glucagon at low glucose concentrations were discussed.
Calcitonin Gene-Related Peptide Mediated Neurogenic Vasorelaxation in the Isolated Canine Lingual Artery
1995, The Japanese Journal of Pharmacology
The nature of neurogenic relaxation was investigated in ring preparations of canine lingual artery. In all experiments, the preparations were previously treated with guanethidine (5×10⁻⁶ M) to block neurogenic constrictor responses. In the presence of norepinephrine (10⁻⁵ M) to induce tone, electrical stimulation (10 V, 4 to 16 Hz, for 45 sec) produced relaxation of the rings in an endothelium-independent fashion. The relaxant response in endothelium-denuded rings was not changed by propranolol (10⁻⁵ M), and atropine (10⁻⁵ M) did not affect the relaxation elicited by electrical stimulation in endothelium-intact rings. N^G-monomethyl-L-arginine (10⁻⁴M) or N^G-nitro-L-arginine methyl ester (10⁻⁴M), a nitric oxide (NO) synthase inhibitor, had no effect on the electrical stimulation-induced relaxation of endothelium-denuded rings. Human calcitonin gene-related peptide (CGRP)-(8-37) (2×l0^_8M), a CGRP₁-receptor antagonist, inhibited neurogenic relaxation of endothelium-denuded rings; substance P (10⁻⁶ M) failed to mimic the observed effect of electrical stimulation. The demonstrated effect of electrical stimulation was inhibited by glibenclamide (10⁻⁵ M), but not tetraethylammonium (2 × 10⁻⁴ M); glibenclamide abolished the relaxation in response to exogenous CGRP or the ATP-sensitive K⁺ channel opener cromakalim (10⁻⁶ M) in endothelium-denuded rings. Moreover, tetrodotoxin (3.13 × 10⁻⁶M) inhibited the relaxation of endothelium-denuded rings induced by electrical stimulation. The relaxation was selectively inhibited when endogenous CGRP had been depleted from perivascular nerves by capsaicin (10^_6M). These results suggest that CGRP, but not NO, released from non-adrenergic non-cholinergic nerves by electrical stimulation produces relaxation of canine lingual artery that is mediated by activation of CGRP₁ receptors.
Guide to the pharmacology of mitochondrial potassium channels
2017, Handbook of Experimental Pharmacology
Mitochondrial channels: Ion fluxes and more
2014, Physiological Reviews

View all citing articles on Scopus

View full text

A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel

Abstract

J. Biol. Chem.

Pflügers Arch.

Pflügers Arch.

Am. J. Physiol.

Nature

Pflügers Arch.

A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K⁺ channel