Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of 15 different potassium channel genes in rat atrial and ventricular muscle was quantitatively compared by use of an RNase protection assay. Of these genes, only five, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2, were expressed at significant levels in cardiac muscle. In comparisons of atrial and ventricular RNA samples, transcripts from the Kv1.2 and Kv4.2 genes showed the largest differences in relative abundance. There was an approximately twofold decrease in total Kv4 subfamily mRNA expression in atrial muscle relative to ventricular muscle and a 70% increase in total Kv1 subfamily mRNA. Variation of potassium channel mRNA expression within the left ventricular wall was also examined. There was a large gradient of Kv4.2 expression across the ventricular wall, and Kv4.2 expression in epicardial muscle was more than eight times higher than in papillary muscle. Other potassium channel genes were expressed at relatively uniform levels across the ventricular wall. The results suggest that transcriptional regulation makes a significant contribution to the control of potassium channel expression in cardiac muscle and to the variation of the electrophysiological phenotype of myocytes from different regions of the myocardium.
 ...
PMID:Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats. 803 39

The expression of eighteen different voltage-activated potassium channel genes in rat sympathetic ganglia was quantitatively analysed using an RNase protection assay. Eleven alpha-subunit genes and two beta-subunit genes were expressed in sympathetic ganglia. The relative level of potassium channel mRNA expression was compared between the superior cervical ganglion (SCG) and two preverteabral sympathetic ganglia, the coeliac ganglion (CG) and the superior mesenteric ganglion (SMG). Four mRNAs were differentially expressed: Kv1.2, Kv1.4, Kv2.2 and Kv beta 1. Transcripts from all four genes were more abundant in the prevertebral ganglia. From comparisons with previous electrophysiological studies it was concluded that genes encoding the channels underlying the M-current and D2-current, which are both prominent in sympathetic neurons, have yet to be identified. It was also concluded that members of the Kv4 family are likely to underlie the low-threshold A-current in sympathetic neurons.
 ...
PMID:Potassium channel mRNA expression in prevertebral and paravertebral sympathetic neurons. 871 62

Left ventricular (LV) remodeling after experimental myocardial infarction (MI) is associated with hypertrophy of noninfarcted myocardium and electrophysiological alterations. We have recently shown that post-MI hypertrophied LV myocytes have prolonged action potential duration (APD) and generate triggered activity from early afterdepolarizations. The prolonged APD was attributed to decreased density of the two outward K+ currents, I(to)-fast (I(to)-f) and I(to)-slow (I(to)-s), rather than changes in the density and/or kinetics of the L-type Ca2+ current. The changes in ionic current density may be related to alterations in the expression and levels of ion channel proteins. To test this hypothesis, rats underwent either left anterior descending coronary artery (LAD) ligation (post-MI group [n = 10]) or sham surgery (sham group [n = 10]). Three weeks later transcripts from the noninfarcted LV myocardium in the post-MI group (n = 6) and LV myocardium of the sham group (n = 6) were analyzed by RNase protection assay. Expressions of five K+ channel subunit mRNAs (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) reported in the rat ventricle were analyzed. Compared with the sham group, expressions of Kv1.4, Kv2.1 (putative I(to)-s), and Kv4.2 (putative I(to)-f) channel subunit mRNAs were significantly decreased by 60% (P < .03), 54% (P < .005), and 53% (P < .002), respectively, in the post-MI group. There was no significant change in the Kv1.2 and Kv1.5 mRNA levels. Western blotting demonstrated a similar decrease in the Kv2.1 and Kv4.2 immunoreactive protein levels (43% [P < .03] and 67% [P < .003], respectively [n = 4]) and no significant change in Kv1.5 immunoreactive protein level. Our results strongly correlate with the electrophysiological findings in this model and show that transcriptional regulation in the post-MI remodeled rat LV is distinct for each voltage-gated K+ channel subunit. These findings provide, at least in part, the molecular basis for the electrophysiological alterations observed in this model.
 ...
PMID:Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. 883 90

In the experiments here, the developmental expression of the functional Ca(2+)-independent, depolarization-activated K+ channel currents, Ito and IK, and of the voltage-gated K+ channel (Kv) alpha subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2 in rat ventricular myocytes were examined quantitatively. Using the whole-cell patch clamp recording method, the properties and the densities of Ito and IK in ventricular myocytes isolated from postnatal day 5 (P5), 10 (P10), 15 (P15), 20 (P20), 25 (P25), 30 (P30), and adult (8-12 wk) rats were characterized and compared. These experiments revealed that mean Ito densities increase fourfold between birth and P30, whereas IK densities vary only slightly. Neither the time- nor the voltage-dependent properties of the currents vary measurably, suggesting that the subunits underlying functional Ito and IK channels are the same throughout postnatal development. In parallel experiments, the developmental expression of each of the voltage-gated K+ channel alpha subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2, was examined quantitatively at the mRNA and protein levels using subunit-specific probes. RNase protection assays revealed that Kv1.4 message levels are high at birth, increase between P0 and P10, and subsequently decrease to very low levels in adult rat ventricles. The decrease in message is accompanied by a marked reduction in Kv1.4 protein, consistent with our previous suggestion that Kv1.4 does not contribute to the formation of functional K+ channels in adult rat ventricular myocytes. In contrast to Kv1.4, the mRNA levels of Kv1.2, Kv1.5, Kv2.1, and Kv4.2 increase (three- to five-fold) between birth and adult. Western analyses, however, revealed that the expression patterns of these subunits proteins vary in distinct ways: Kv1.2 and Kv4.2, for example, increase between P5 and adult, whereas Kv1.5 remains constant and Kv2.1 decreases. Throughout development, therefore, there is a mismatch between the numbers of Kv alpha subunits expressed and the functional voltage-gated K+ channel currents distinguished electrophysiologically in rat ventricular myocytes. Alternative experimental approaches will be required to define directly the Kv alpha subunits that underlie functional voltage-gated K+ channels in these (and other) cells. In addition, the finding that Kv alpha subunit protein expression levels do not necessarily mirror mRNA levels suggests that caution should be exercised in attempting functional interpretations of observed changes in mRNA levels alone.
 ...
PMID:Developmental analysis reveals mismatches in the expression of K+ channel alpha subunits and voltage-gated K+ channel currents in rat ventricular myocytes. 892 66

Hypertension-induced cardiac hypertrophy is associated with alterations in ventricular action potentials. To understand molecular mechanisms underlying this electrical abnormality, expression of cardiac voltage-gated K+ channel subunit genes was examined in ventricles of renovascular hypertensive rats. While generating a rat Kv4.3 probe, we discovered a previously unreported 19-amino acid insertion in the C-terminal intracellular region of the channel subunit. RNase protection assays indicated that this novel isoform is predominant in rat lung and heart. Effects of renovascular hypertension were then determined by using renal artery clipping models: two-kidney, one clip (2K-1C) rats, a model of high-renin hypertension with a normal plasma volume, and one-kidney, one clip (1K-1C) rats, a model of normal renin with a raised plasma volume. Expression of Kv4.2 and Kv4.3 mRNAs was diminished by > 50% in ventricles of 2K-1C rats; however, no changes in the expression of Kv1.2, Kv1.4, Kv1.5, Kv2.1, or KvLQT1 mRNAs were detected. Similar downregulation of Kv4.2 and Kv4.3 mRNAs was detected in 1K-1C rats. Chronic administration of captopril, an angiotensin-converting enzyme inhibitor, blocked the development of hypertension and the suppression of Kv4 subfamily channel mRNA expression in 2K-1C rats. Furthermore, captopril administration to sham-operated rats significantly increased Kv4.2 mRNA. These results indicate that renovascular hypertension causes specific reductions in Kv4 subfamily channel mRNA expression and that this effect is likely to be mediated primarily by an increase in cardiac afterload.
 ...
PMID:Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. 931 34

Few potassium channel genes have been isolated in the guinea-pig despite detailed electrophysiological characterization of potassium channels in the guinea-pig heart. We obtained partial clones of Shaker-type potassium channel genes in the guinea-pig and demonstrated their tissue distribution. Partial clones of the Shaker-type potassium channel genes were obtained by RT-PCR or genomic PCR. mRNA expression was measured by RNase protection assays in the heart, brain, and skeletal muscle. Three of the five obtained channel genes were expressed in the guinea-pig heart; Kv1.2, Kv1.3, and Kv1.6. Kv 1.6 expression was markedly at a higher level in the atrium than in the ventricle. Expression of the channel genes in the guinea-pig was different from that in human and rat, which may contribute to the species-specific action potential waveform.
 ...
PMID:Expression of Shaker-type voltage-gated potassium channel genes in the guinea-pig. 952 53

Effects of thyroid hormones on cardiac function or rhythm have been known; however, the mechanism is still unclear. In the present study examined were effects of triiodethyronine (T3) on voltage-gated potassium channel gene expression in rat heart since the potassium channels were presumed to modulate cardiac functions. The mRNA expression of five voltage-gated potassium channel gene alpha subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) in heart was examined by ribonuclease protection assay in rats which were treated with T3 or propylthyouracil (PTU). All these genes except Kv1.4 mRNA were apparently expressed in the normal rat heart ventricle. Kv1.2 mRNA expression in ventricle was markedly suppressed by T3-treatment and enhanced by PTU-treatment. Interestingly, upregulation of Kv1.4 mRNA expression and downregulation of Kv1.5 mRNA expression were concomitantly induced in the ventricle by the PTU-treatment. In addition, the downregulation of the ventricular Kv1.5 mRNA expression induced by PTU was restored by T3 replacement. No changes of Kv2.1 and Kv4.2 mRNA expression were observed in the ventricles by the T3- or PTU-treatment. In heart atrium the same findings were observed. Kv1.4 mRNA expression, which was detectable in control rat atrium, also decreased significantly by T3-treatment. In contrast, no changes of Kv1.2, Kv1.4, and Kv1.5 mRNA expression in rat brains were induced by T3-treatment. These findings suggest that thyroid hormone specifically influences mRNA expression of Shaker-related potassium channel genes in rat hearts through a common T3 receptor-mediated regulation at a transcriptional level.
 ...
PMID:Thyroid hormone regulates expression of shaker-related potassium channel mRNA in rat heart. 953 13

The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K(+) channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 +/- 0.01 vs. 0.58 +/- 0.03 ms (n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 +/- 2.6 ms vs. 31.5 +/- 5.8 ms (n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 +/- 8.9 ms vs. 110.0 +/- 4.2 ms (n = 6); P < 0.05] and corrected Q-T interval [Q-T(c); control vs. MCT: 8.4 +/- 0. 7 ms vs. 10.2 +/- 0.4 ms (n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4. 3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 +/- 10, 76 +/- 3, 58 +/- 5, 81 +/- 5, and 45 +/- 12%, respectively (n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 +/- 0.28 vs. 0.88 +/- 0.44 (arbitrary units) (n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 +/- 0.25 vs. 0.87 +/- 0.18 (n = 3), NS; Kv1.4: 1.0 +/- 0.22 vs. 1.27 +/- 0.37 (n = 3), NS; Kv1.5: 1.0 +/- 0.16 vs. 0.91 +/- 0.28 (n = 3), NS; Kv2.1: 1.0 +/- 0.26 vs. 0.99 +/- 0.25 (n = 3), NS; Kv4.2: 1.0 +/- 0.15 vs. 1.22 +/- 0.28 (n = 3), NS; Kv4.3: 1.0 +/- 0.20 vs. 1.21 +/- 0.28 (n = 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K(+) channels.
 ...
PMID:Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy. 1056 25

Previous studies have raised the possibility that a decrease in voltage-gated K+ currents may contribute to hyperexcitability of injured dorsal root ganglion (DRG) neurons and the emergence of neuropathic pain. We examined the effects of axotomy on mRNA levels for various Kv1 family subunits and voltage-gated K+ currents in L4-L5 DRG neurons from sham-operated and sciatic nerve-transected rats. RNase protection assay revealed that Kv1.1 and Kv 1.2 mRNAs are highly abundant while Kv1.3, Kv1.4, Kv1.5 and Kv1.6 mRNAs were detected at lower levels in L4-L5 DRGs from sham and intact rats. Axotomy significantly decreased Kv1.1, Kv1.2, Kv1.3 and Kv1.4 mRNA levels by approximately 35%, approximately 60%, approximately 40% and approximately 80%, respectively, but did not significantly change Kv1.5 or Kv1.6 mRNA levels. Patch clamp recordings revealed two types of K+ currents in small-sized L4-L5 DRG neurons: sustained delayed rectifier currents elicited from a -40 mV holding potential and slowly inactivating A-type currents that was additionally activated from a -120 mV holding potential. Axotomy decreased both types of K+ currents by 50-60% in injured DRG neurons. In addition, axotomy increased the alpha-dendrotoxin sensitivity of the delayed rectifier, but not slow A-type K+ currents in injured DRG neurons. These results suggest that Kv1.1 and Kv1.2 subunits are major components of voltage-gated K+ channels in L4-L5 DRG neurons and that the decreased expression of Kv1-family subunits significantly contributes to the reduction and altered kinetics of Kv current in axotomized neurons.
 ...
PMID:Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy. 1475 Dec 80