KIR6.1 K+ channel subunits are expressed in mouse ventricular myocytes and associate with the actin cytoskeleton

Rosner, Erika; Lopez, Gwen; Nakamura, Tomoe Y.; Porter, Lisa A.; Pountney, David; Coetzee, William A.

doi:10.1016/s0022-2828(01)90407-9

Cited by 2 publications

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“…In the mouse heart, this channel is expressed in mitochondria (Lacza et al 2003) and also in the coronary arteries (Miki et al 2002). It has been suggested from Western blot analysis that Kir6.1 subunits are present in the plasma membrane of murine cardiomyocytes (Rosner et al 2002). Kir6.1‐null mice (Miki et al 2002) exhibit a normal pinacidil‐induced glibenclamide‐sensitive outward current in their cardiomyocytes, suggesting that Kir6.1 is not a component of the sarcolemmal K ATP channel.…”

Section: Discussionmentioning

confidence: 99%

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Marionneau

Couette

Liu

et al. 2004

The Journal of Physiology

298

263

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Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle (C t ) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.

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Section: Discussionmentioning

confidence: 99%

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Marionneau

Couette

Liu

et al. 2004

The Journal of Physiology

298

263

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Distribution of Kir6.0 and SUR2 ATP-sensitive potassium channel subunits in isolated ventricular myocytes

Singh¹

2003

Journal of Molecular and Cellular Cardiology

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The subcellular distribution of K ATP channel subunits in rat isolated ventricular myocytes was investigated using a panel of subunit specific antisera. Kir6.1 subunits were associated predominantly with myofibril structures and were co-localized with the mitochondrial marker MitoTracker red (correlation coefficient (cc) = 0.63 ± 0.05 ).Anti-Kir6.1 antibodies specifically recognized a polypeptide of 48 kDa in mitochondrial membrane fractions consistent with the presence of Kir6.1 subunits in this organelle.Both Kir6.2 and SUR2A subunits were distributed universally over the sarcolemma.Lower intensity antibody associated immunofluorescence was detected intracellularly, which was correlated with the distribution of MitoTracker red in both cases (cc, Kir6.2, 0.56 ± 0.05; SUR2A, 0.61 ± 0.06). A polypeptide of 40 kDa was recognized by antiKir6.2 subunit antibodies in Western blots of both microsomal and mitochondrial membrane fractions consistent with the presence of this subunit in the sarcolemma and mitochondria. Similarly, SUR2A and SUR2B subunits were detected in Western blots of microsomal membrane proteins consistent with a sarcolemmal localization for these polypeptides. SUR2B subunits were shown in confocal microscopy to co-localize strongly with t-tubules (cc, 0.81 ± 0.05). Together the results indicate that Kir6.2 and SUR2A subunits predominate in the sarcolemma of ventricular myocytes consistent with a Kir6.2/SUR2A subunit combination in the sarcolemmal K ATP (sarcK ATP ) channel.Kir6.1, Kir6.2 and SUR2A subunits were demonstrated in mitochondria. Combinations of these subunits would not explain the reported pharmacology of the mitochondrial K ATP (mitoK ATP ) channel (Lui et al. 2001. Mol. Pharmacol. 59:225-230) suggesting the possibility of further unidentified components of this channel.3

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KIR6.1 K+ channel subunits are expressed in mouse ventricular myocytes and associate with the actin cytoskeleton

Cited by 2 publications

References 0 publications

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Distribution of Kir6.0 and SUR2 ATP-sensitive potassium channel subunits in isolated ventricular myocytes

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