, and Itsuo Kodama. Ca v3.2 subunit underlies the functional T-type Ca 2ϩ channel in murine hearts during the embryonic period.

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Abstract. Re-expression of fetal genes has been considered to underlie ionic remodeling in diseased heart. T-type Ca 2+ channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca 2+ channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca 2+ channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca 2+ channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni 2+ at low concentrations. The current was not detectable in the adult stage. Ca v 3.2 (α 1H ) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca v 3.1 (α 1G ) increases from 9.5 to 18 dpc, but remains at low level compared with Ca v 3.2. In contrast, Ca v 3.1 is greater than Ca v 3.2 at the adult stage. In MI, Ca v 3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca v 3.2 mRNA correlates positively with BNP mRNA. In AOB, these correlations are weak. We also analyzed the neuron-restrictive silencer factor (NRSF) in these hearts because it is the suppressor of transcription of the fetal cardiac gene program. The negative correlation between NRSF and BNP was stronger in MI than in AOB. Our findings show that Ca v 3.2 underlies the functional T-type Ca 2+ channel in embryonic heart and suggest that NRSF may regulate Ca v 3.2 expression in diseased hearts.

ap junctions are specialized membrane regions consisting of groups of channels that directly connect the cytoplasmic components of adjacent cells and enable intercellular communication with respect to the exchange of ions and small (<1 kDa) molecules. 1 Gap junctions are composed of transmembrane proteins that belong to the connexin family. The principal gap junctional protein expressed in ventricles of the mammalian heart is connexin43 (Cx43), although connexin40, connexin45 and connexin 30.2 (and its human ortholog, connexin31.9) are also expressed in other regions of the heart. [2][3][4] Remodeling of gap junction in the heart is an important feature of the structural substrates for conduction disturbance and arrhythmogenesis under various pathological conditions including myocardial ischemia, infarction and hypertrophy. [2][3][4][5][6][7][8] In our previous immunohistochemical studies on rats with pressure overload-induced ventricular hypertrophy, we have shown that the cellular distribution of gap junctions are altered; in normal ventricles Cx43 gap junctions are largely confined to the intercalated disks at the cell termini, but in hypertrophied ventricles, Cx43 gap junctions are displaced from the intercalated disks and widely distributed. 9,10 Cx43 is a phosphoprotein, and the phosphorylation/dephosphorylation of Cx43 plays important roles in the regulation of protein turnover dynamics (trafficking, plaque assembly, internalization and degradation) as well as channels gating properties. 1,[11][12][13][14] In the hearts subjected to acute ischemia, [15][16][17] and in non-ischemic heart failure, 18 as well as in dilated cardiomyopathy, 19 dephosphorylation of Cx43 was shown to play an important role in its disorganization and electrical uncoupling of ventricular cells under the pathological conditions. It is well known that ventricular hypertrophy is associated with the activation or inhibition of various types of protein kinases and/or phosphatases. We, therefore, hypothesized that phosphorylation/dephosphorylation of Cx43 could also be involved in the disorganization of Cx43 gap junctions in the pressure-overload ventricular hypertrophy.In the present study, we have investigated the expression and distribution of Cx43 and its phosphorylation state in hypertrophied ventricles of rats with monocrotaline (MCT)-induced pulmonary hypertension by immunoconfocal and electron microscopy, as well as immunoblotting using isoform-specific antibodies. Background Altered expression and distribution of gap junctions might provide substrates for abnormal conduction and arrhythmogenesis in the heart, but little is known about the regulation of gap junctions under pathological conditions. The organization and phosphorylation state of connexin43 (Cx43) in ventricular hypertrophy will be investigated. Methods and ResultsRight ventricular (RV) hypertrophy was induced in rats by treatment with monocrotaline. Subcellular Cx43 distribution was assessed by immunoconfocal and electron microscopy. Immunolabeling of Cx43 was conf...

Aim: Cerebral white matter lesions (WML) are known to increase with age, as is left ventricular (LV) diastolic dysfunction with normal contraction. Although aging is a common risk factor, the link between these diseases is not fully understood. The aim was to clarify this relationship, using the ratio between early diastolic mitral inflow and early diastolic mitral annular tissue velocity (E/E'). E/E' measured by tissue Doppler echocardiography offers an indicator of the severity of LV diastolic dysfunction, reflecting both diastolic LV stiffness and diastolic LV filling pressure. Methods:Participants comprised 75 patients aged between 65 and 75 years with normal LV contraction and no signs or history of symptomatic heart failure, ischemic heart diseases, atrial fibrillation, stroke, or cognitive dysfunction. The volume of WML was quantified on brain magnetic resonance imaging. Results:The participants were classified into three groups: Low E/E', E/E' ≤ 8; Middle E/E', 8 < E/E' < 15; and High E/E', E/E' ≥ 15. WML volume was 3.6 ± 3.0 mL in Low E/E', 5.4 ± 6.5 mL in Middle E/E' and 12.0 ± 11.0 mL in High E/E', increasing significantly with increased diastolic LV stiffness (Low vs High, P = 0.034; Middle vs High, P = 0.016). Linear regression analysis showed the positive association between the volume of WML and E/E' ratio (r = 0.377, P = 0.0009). Conclusions:This investigation identified an association between LV diastolic dysfunction and WML. Further investigations are required to clarify whether there is a direct association between the two diseases. Geriatr Gerontol Int 2014; 14 (Suppl. 2): 71-76.Keywords: cerebral white matter lesions, left ventricular diastolic dysfunction, ratio of early diastolic mitral inflow to early diastolic mitral annular tissue velocity.

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Type 2 diabetes mellitus accelerates loss of muscle mass and strength. Patients with Alzheimer’s disease (AD) also show these conditions, even in the early stages of AD. The mechanism linking glucose management with these muscle changes has not been elucidated but has implications for clarifying these associations and developing preventive strategies to maintain functional capacity. This study included 69 type 2 diabetes patients with a diagnosis of cognitive impairment (n = 32) and patients with normal cognition (n = 37). We investigated the prevalence of sarcopenia in diabetes patients with and without cognitive impairment and examined the association of glucose alterations with sarcopenia. Daily glucose levels were evaluated using self-monitoring of blood glucose, and we focused on the effects of glucose fluctuations, postprandial hyperglycemia, and the frequency of hypoglycemia on sarcopenia. Diabetes patients with cognitive impairment displayed a high prevalence of sarcopenia, and glucose fluctuations were independently associated with sarcopenia, even after adjusting for glycated hemoglobin A1c (HbA1c) levels and associated factors. In particular, glucose fluctuations were significantly associated with a low muscle mass, low grip strength, and slow walking speed. Our observation suggests the importance of glucose management by considering glucose fluctuations to prevent the development of disability.