Theophylline affects three different potassium currents in dissociated rat cortical neurones.

Munakata, Mitsutoshi; Akaike, Norio

doi:10.1113/jphysiol.1993.sp019918

Cited by 22 publications

(12 citation statements)

References 37 publications

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“…Second, in the present experiments the Ca 2+ chelator BAPTA was used in the internal solution in order to reduce calcium-activated potassium currents. However, as BAPTA has been shown to gradually suppress the I M [19] , this may adversely infl uence our results, and may well be the reason M channel kinetics in OHC are less apparent than in, for instance, superior cervical ganglion neurons [10] .…”

Section: Discussionmentioning

confidence: 72%

An M-Like Potassium Current in the Guinea Pig Cochlea

Guihua

Moore²,

Ulfendahl³

et al. 2005

ORL

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Potassium M currents play a role in stabilizing the resting membrane potential. These currents have previously been identified in several cell types, including sensory receptors. Given that maintaining membrane excitability is important for mechano-electrical transduction in the inner ear, the presence of M currents was investigated in outer hair cells isolated from the guinea pig hearing organ. Using a pulse protocol designed to emphasize M currents with the whole-cell patch-clamp technique, voltage- and time-dependent, non-inactivating, low-threshold currents (the hallmarks of M currents) were recorded. These currents were significantly reduced by cadmium chloride. Results from RT-PCR analysis indicated that genes encoding M channel subunits KCNQ2 and KCNQ3 are expressed in the guinea pig cochlea. Our data suggest that guinea pig outer hair cells express an M-like potassium current that, following sound stimulation, may play an important role in returning the membrane potential to resting level and thus regulating outer hair cell synaptic mechanisms.

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Section: Discussionmentioning

confidence: 72%

An M-Like Potassium Current in the Guinea Pig Cochlea

Guihua

Moore²,

Ulfendahl³

et al. 2005

ORL

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“…A similar lack of convulsant effects has been reported in studies using CPT, whereas theophylline reliably demonstrates a potent convulsant effect. As DPCPX does not cause convulsions in vivo even at very high doses, the convulsioninducing effect of theophylline may be related more to its reported ability to block K + channels (Munakata and Akaike 1993) or to phosphodiesterase inhibition than to an antagonism at adenosine A1 receptors.…”

Section: Discussionmentioning

confidence: 95%

Alkylxanthine adenosine antagonists and epileptiform activity in rat hippocampal slices in vitro

Chesi

Stone

1997

Exp Brain Res

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Despite its potent proconvulsant effects in vitro, the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) does not induce seizures when administered in vivo. This contrasts with the effects of less selective adenosine antagonists such as theophylline or cyclopentlytheophylline, and led us to reexamine the nature of DPCPX-induced epileptiform activity. In the present study, we report that proconvulsant effects of bath-applied DPCPX in rat hippocampal slices are only observed after a preceding stimulus such as NMDA receptor activation or brief tetanic stimulation. While this may be due to the absence of a basal "purinergic tone", the relatively high interstitial concentrations of adenosine present in the slice suggest that access of the drug to A1 receptors may instead be prevented by tightly coupled endogenous adenosine, with the ternary adenosine-A1 receptor-G protein complex stabilised in the high-affinity conformation by a coupling cofactor. This implies that a substantial percentage of adenosine A1 receptors are inactive under physiological conditions, but that access of adenosine A1 receptor antagonists may be facilitated under pathological conditions. Once induced, DPCPX-evoked spiking persists for long periods of time. A "kindling" effect of A1 receptor blockade is unlikely, since persistent spiking is not usually observed with less selective A1 antagonists even after prolonged application. Alternatively, endogenous adenosine released during increased neuronal activity may activate A2 receptors during selective A1 blockade. The most important factor determining the duration of DPCPX-induced spiking, however, may be a persistence of the drug in the tissue and subsequent access to the A1 receptor via a membrane-delineated pathway, since DPCPX-induced spiking could be shown to decrease markedly after a transient superfusion of theophylline. This hypothesis, which implies that the apparent affinity of adenosine antagonists for the A1 receptor is in part a function of their membrane partitioning coefficient, is supported by a close correlation between alkylxanthine logP values obtained from the literature and their Ki value at A1 receptors, but not at the enzyme phosphodiesterase, whose xanthine binding site is presented to the cytosol. The implications for the therapeutic value of purinergic drugs are discussed.

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“…Single neocortical neurons were isolated from 12-to 18-day-old Wistar rats of both sexes, as previously described (Munakata and Akaike 1993). Briefly, pentobarbital-anesthetized rats were decapitated, the brains were removed, and a microslicer (DTK-1000, Dosaka EM, Kyoto, Japan) was used to cut coronal slices (400 μ m thickness) in incubation solution saturated with 5% CO 2 and 95% O 2 .…”

Section: Methodsmentioning

confidence: 99%

.BETA.-Phenylethylamine Inhibits K+ Currents in Neocortical Neurons of the Rat: A Possible Mechanism of .BETA.-phenylethylamine-induced Seizures

Kitamura

Munakata

Haginoya

et al. 2008

Tohoku J. Exp. Med.

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β -Phenylethylamine (β -PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. β -PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but β -PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which β -PEA induces convulsions, we examined the effect of β -PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of β -PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 μ M. These currents suppressed by β -PEA consisted of two K + currents: a time-and voltagedependent K + current (M-current) and a leakage K + current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K + current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose β -PEA.β -phenylethylamine; M-current; patch-clamp; seizure.

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Theophylline affects three different potassium currents in dissociated rat cortical neurones.

Abstract: SUMMARY1. The effects of theophylline in pyramidal neurones acutely dissociated from the rat frontal cortex were investigated in the whole-cell configuration, using the nystatin-perforated patch-clamp technique.2.

Cited by 22 publications

References 37 publications

An M-Like Potassium Current in the Guinea Pig Cochlea

An M-Like Potassium Current in the Guinea Pig Cochlea

Alkylxanthine adenosine antagonists and epileptiform activity in rat hippocampal slices in vitro

.BETA.-Phenylethylamine Inhibits K+ Currents in Neocortical Neurons of the Rat: A Possible Mechanism of .BETA.-phenylethylamine-induced Seizures

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