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Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased [Ca.sup.2+] transients and sarcoplasmic reticulum (SR) [Ca.sup.2+] uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased [Na.sup.+]/[Ca.sup.2+] exchanger, [beta]-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR [Ca.sup.2+] cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload. calcium | cardiac hypertrophy | sarcoplasmic reticulum | deiodinase | transgenic mice

Research has been conducted on the PI3K/PTEN signaling pathways. The study of cardiomycete-specific inactivation of tumor suppressor PTEN leading to cardiac contractility disease has been carried out and the role of PTEN in cardiomyocyte hypertrophy and GPCR signaling and the functions of PI3K/PTEN pathway in heart muscle contractility modulation are discussed.

Transient outward [K.sup.+] current density ([I.sub.to]) has been shown to vary between different regions of the normal myocardium and to be reduced in heart disease. In this study, we measured regional changes in action potential duration (APD), [I.sub.to], and intracellular [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At +40 mV, [I.sub.to] density in sham-operated hearts was significantly higher (P < 0.01) in the RVW (15.0 [+ or -] 0.8 pA/pF, n = 47) compared with the SEP (7.0 [+ or -] 1.1 pA/pF, n = 18). After MI, [I.sub.to] density was not reduced in SEP myocytes but was reduced (P < 0.01) in RVW myocytes (8.7 [+ or -] 1.0 pA/pF, n = 26) to levels indistinguishable from post-MI SEP myocytes. These changes in [I.sub.to] density correlated with Kv4.2 (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was significantly higher in the RVW compared with the SEP and increased significantly after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas peak [[[Ca.sup.2+]].sub.i] transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [[[Ca.sup.2+]].sub.i] transients were eliminated by MI. Our results demonstrate that the significant regional differences in [I.sub.to] density, APD, and [[[Ca.sup.2+]].sub.i] between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI. right ventricle; septum; heart disease; contraction

Research was conducted to examine the effects of local anesthetics on rat skeletal muscle Na+ channels containing the equine hyperkalemic periodic paralysis mutation when expressed in Xenopus oocytes. Equine mutation was characterized by episodes of myotonia, weakness and flaccid paralysis in association with elevated serum K+ levels. Results indicate that local anesthetics could promote inactivation and restore normal Na+ channel gating properties.