Distribution and localization of a G protein‐coupled inwardly rectifying K<sup>+</sup> channel in the rat

Karschin, Christine; Schultze-Seemann, Wolfgang; Dascal, Nathan; Lester, Henry A.; Davidson, Norman; Karschin, Andreas

doi:10.1016/0014-5793(94)00590-7

Cited by 82 publications

(51 citation statements)

References 19 publications

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“…Kir2.0 or Kir3.0, have never been reported. As mentioned in a previous study, we did not detect significant levels of Kirl.l (ROMK1) transcripts in the brain [20], but rather in the outer medulla of the rat kidney, suggesting an insignificant role in native brain KATP channels. In contrast, we found the ubiquitous Kiro.l (UKATP-1; [21]), of which moderate mRNA levels in the brain were detected in the original Northern blots, in a distinct cell population throughout the brain using several different oligonucleotide probes (C. Ecke, unpublished observation).…”

Section: Discussionsupporting

confidence: 60%

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

et al. 1997

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ATP-sensitive K+ channels comprise a complex of at least two proteins: a member of the inwardly rectifying Kir6 family (e.g. Kir6.2) and a sulphonylurea receptor (e.g. SURI) which belongs to the ATP-binding cassette (ABC) superfamily. Using specific radiolabeled antisense oligonucleotides, the cellular localization of both mRNAs was investigated in the rodent brain by in situ hybridization. The distribution of both transcripts was widespread throughout the brain and showed a high degree of overlap with peak expression levels in the hippocampus, neocortex, olfactory bulb, cerebellum, and several distinct nuclei of the midbrain and brainstem, indicating their important role in vital brain function.

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Section: Discussionsupporting

confidence: 60%

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

et al. 1997

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“…Kir3.1 mRNAs are expressed strongly in rat atria but not ventricles, 88,89 and Kir3.1 and Kir3.4 proteins are abundant in the atrium and sparse in the ventricle, 27 consistent with predominantly atrial I KACh expression. 85 Recent work suggests that homomeric Kir3.4 channels may also contribute to atrial I KACh .…”

Section: Ionic Mechanismsmentioning

confidence: 86%

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

Schram

Pourrier

Melnyk

et al. 2002

Circulation Research

378

283

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Abstract-The cardiac electrical system is designed to ensure the appropriate rate and timing of contraction in all regions of the heart, which are essential for effective cardiac function. Well-controlled cardiac electrical activity depends on specialized properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Cardiac electrical specialization was first recognized in the mid 1800s, but over the past 15 years, an enormous amount has been learned about how specialization is achieved by differential expression of cardiac ion channels. More recently, many aspects of the molecular basis have been revealed. Although the field is potentially vast, an appreciation of key elements is essential for any clinician or researcher wishing to understand modern cardiac electrophysiology. This article reviews the major regionally determined features of cardiac electrical function, discusses underlying ionic bases, and summarizes present knowledge of ion channel subunit distribution in relation to functional specialization. Key Words: ion channels Ⅲ molecular biology Ⅲ conduction Ⅲ cardiac arrhythmias Ⅲ antiarrhythmic drugs C ardiac function depends on the appropriate timing of contraction in various regions, as well as on appropriate heart rate. To subserve these functions, electrical activity in each region is adapted to its specialized function. Regionally specialized cardiac electrical function was recognized in the mid 1800s, when Stannius 1 demonstrated that ligatures in the superior vena caval sinus region of the frog caused cardiac asystole, with the sinus continuing to beat. With the widespread application to cardiac ion channel study of patchclamp methodologies in the 1980s and molecular biology in the 1990s, many underlying mechanisms have been unraveled. The present article reviews the major regionally determined features of cardiac electrical function and the present knowledge regarding ionic and molecular bases. Overview of Regional Functional SpecificityFigure 1 illustrates typical regional action potential (AP) properties in the heart. The normal cardiac impulse originates in the sinoatrial node (SAN) and propagates through the atria to reach the atrioventricular node (AVN). From the AVN, electrical activity passes rapidly through the cable-like HisPurkinje system to reach the ventricles, triggering cardiac pumping action. Figure 2 shows the ionic currents involved in a schematic cardiac AP, provides standard abbreviations for currents and their corresponding subunits, and summarizes principal localization data discussed elsewhere in the present review. Ionic and Molecular Basis of Functional Specificity Sinoatrial Node Cellular Electrophysiology and FunctionThe SAN, located in the right atrial (RA) roof between the venae cavae, 2 is specialized for physiological pacemaker function. Heart rate control is achieved through autonomic regulation of SAN pacemaking. SAN APs have a relatively positive maximum diastolic potential (MDP...

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“…GIRK channels are gated by the PTXsensitive G-protein directly (Huang et al, 1995), which couples to a variety of neurotransmitter receptors such as 5-HT 1A , GABA B , m-, k-and d-opioid, a 2 -adrenoceptors and D 2 receptors (Suprenant & North, 1988;Loose & Kelly, 1990;Kim et al, 1995; for review see North, 1989). In situ hybridization experiments showed that GIRK1 is widely distributed in the rat brain including the hippocampus, dorsal raphe, substantia nigra and locus coerulus (Karschin et al, 1994), whereas GIRK2 was found mainly in the cerebellum, substantia nigra, olfactory bulb, cerebral cortex, hippocampus and pons (Kobayashi et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Influence of flupirtine on a G‐protein coupled inwardly rectifying potassium current in hippocampal neurones

Jakob

Krieglstein

1997

British J Pharmacology

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1 Previous studies have shown that¯upirtine, a centrally acting, non-opioid analgesic agent, also exhibits neuroprotective activity in focal cerebral ischaemia in mice and reduces apoptosis induced by NMDA, gp 120 of HIV, prior protein fragment or lead acetate as well as necrosis induced by glutamate or NMDA in cell culture. To study the potential mechanism of the neuroprotective action of¯upirtine, we investigated whether¯upirtine is able to modulate potassium or NMDA-induced currents in rat cultured hippocampal neurones by use of the whole-cell con®guration of the patch-clamp technique. 2 We demonstrated that 1 mM¯upirtine activated an inwardly rectifying potassium current (K ir ) in hippocampal neurones (DI=739+18 pA at 7130 mV; n=10). This e ect was dose-dependent (EC 50 =0.6 mM). The reversal potential for K ir was in agreement with the potassium equilibrium potential predicted from the Nernst equation showing that K ir was predominantly carried by K + . Furthermore, the induced current was blocked completely by Ba 2+ (1 mM), an e ect typical for K ir . 3 The activation of K ir by¯upirtine was largely prevented by pretreatment of the cells with pertussis toxin (PTX) indicating the involvement of a PTX-sensitive G-protein in the transduction mechanism (DI=73+6 pA at 7130 mV; n=8). Inclusion of cyclic AMP in the intracellular solution completely abolished the activation of K ir (n=7). 4 The selective a 2 -adrenoceptor antagonist SKF-86466 (10 mM), the selective 5-HT 1A antagonist NAN 190 as well as the selective GABA B antagonist 2-hydroxysaclofen (10 mM) failed to block the¯upirtine e ect on the inward recti®er. 5 Flupirtine (1 mM) could not change the current induced by 50 mM NMDA. 6 These results show that in cultured hippocampal neurones¯upirtine activates an inwardly rectifying potassium current and that a PTX-sensitive G-protein is involved in the transduction mechanism.

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Distribution and localization of a G protein‐coupled inwardly rectifying K⁺ channel in the rat

Cited by 82 publications

References 19 publications

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

Influence of flupirtine on a G‐protein coupled inwardly rectifying potassium current in hippocampal neurones

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Distribution and localization of a G protein‐coupled inwardly rectifying K+ channel in the rat

Cited by 82 publications

References 19 publications

Overlapping distribution of KATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

Overlapping distribution of KATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function

Influence of flupirtine on a G‐protein coupled inwardly rectifying potassium current in hippocampal neurones

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Distribution and localization of a G protein‐coupled inwardly rectifying K⁺ channel in the rat

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain

Overlapping distribution of K_ATP channel‐forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain