SUMMARY1. The gating and conduction properties of single calcium-release channels of sheep isolated cardiac junctional sarcoplasmic reticulum membranes incorporated into planar phospholipid bilayers were investigated under voltage clamp conditions at temperatures between 4 and 32 'C.2. Single channel conductance was reduced linearly when temperature was decreased from 32 to 5 'C with a Qlo value of 1-5 between 10 and 20 'C. The apparent activation enthalpy for conductance between 32 and 5 'C was 6416+ 1P2 keal/mol. the open and closed lifetime distributions were still best described by three exponentials.7. The net effect of temperature reduction is an increase in calcium current through the channel. This finding is consistent with the suggestion that calcium MS 8607 R. SITSAPESAN AND OTHERS release from the SR is a major factor in the initiation of rapid cooling contractures of mammalian cardiac muscle preparations.

4 17P-Oestradiol (10 and 30 SM) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]0, dihydropyridines and isoprenaline, to 59 ± 3% and 39 + 5% (n = 7-9, P<0.01) respectively, without producing any significant change in the shape of the current-voltage relationship.5 The recovery time of ICa from inactivation was delayed by 17p-oestradiol (10 tiM). The inhibitory effect of 17p-oestradiol on ICa was less at a holding potential of -80 mV than at -40 mV.

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Background-Cardiomyocyte surface morphology and T-tubular structure are significantly disrupted in chronic heart failure, with important functional sequelae, including redistribution of sarcolemmal ␤ 2 -adrenergic receptors (␤ 2 AR) and localized secondary messenger signaling. Plasticity of these changes in the reverse remodeled failing ventricle is unknown. We used AAV9.SERCA2a gene therapy to rescue failing rat hearts and measured z-groove index, T-tubule density, and compartmentalized ␤ 2 AR-mediated cAMP signals, using a combined nanoscale scanning ion conductance microscopy-Förster resonance energy transfer technique. Methods and Results-Cardiomyocyte surface morphology, quantified by z-groove index and T-tubule density, was normalized in reverse-remodeled hearts after SERCA2a gene therapy. Recovery of sarcolemmal microstructure correlated with functional ␤ 2 AR redistribution back into the z-groove and T-tubular network, whereas minimal cAMP responses were initiated after local ␤ 2 AR stimulation of crest membrane, as observed in failing cardiomyocytes. Improvement of ␤ 2 AR localization was associated with recovery of ␤AR-stimulated contractile responses in rescued cardiomyocytes. Retubulation was associated with reduced spatial heterogeneity of electrically stimulated calcium transients and recovery of myocardial BIN-1 and TCAP protein expression but not junctophilin-2. Conclusions-In summary, abnormalities of sarcolemmal structure in heart failure show plasticity with reappearance of z-grooves and T-tubules in reverse-remodeled hearts. Recovery of surface topology is necessary for normalization of ␤ 2 AR location and signaling responses. (Circ Heart Fail. 2012;5:357-365.)