Rem-GTPase regulates cardiac myocyte L-type calcium current

Rationale: The L-type calcium channels (LTCC) are critical for maintaining Ca²⁺-homeostasis. In heterologous expression studies, the RGK-class of Ras-related G-proteins regulates LTCC function; however, the physiological relevance of RGK–LTCC interactions is untested.

Objective: In this report we test the hypothesis that the RGK protein, Rem, modulates native Ca²⁺ current (I_Ca,L) via LTCC in murine cardiomyocytes.

Methods and Results: Rem knockout mice (Rem^?/?) were engineered, and I_Ca,L and Ca²⁺-handling properties were assessed. Rem^?/? ventricular cardiomyocytes displayed increased I_Ca,L density. I_Ca,L activation was shifted positive on the voltage axis, and β-adrenergic stimulation normalized this shift compared with wild-type I_Ca,L. Current kinetics, steady-state inactivation, and facilitation was unaffected by Rem^?/?. Cell shortening was not significantly different. Increased I_Ca,L density in the absence of frank phenotypic differences motivated us to explore putative compensatory mechanisms. Despite the larger I_Ca,L density, Rem^?/? cardiomyocyte Ca²⁺ twitch transient amplitude was significantly less than that compared with wild type. Computer simulations and immunoblot analysis suggests that relative dephosphorylation of Rem^?/? LTCC can account for the paradoxical decrease of Ca²⁺ transients.

Conclusions: This is the first demonstration that loss of an RGK protein influences I_Ca,L in vivo in cardiac myocytes.     

Increase of atrial ANP release by 2,3-butanedione monoxime in beating rabbit atria

2,3-Butanedione monoxime (BDM) is a chemical phosphatase and has been known to dissociate mechanical contraction in the excitation–contraction coupling via inhibition of myofibrillar ATPase. BDM has also been found to decrease sarcolemmal L-type Ca²⁺ channel activity and intracellular Ca²⁺ in cardiac myocytes. It has been shown that Ca²⁺ entry via L-type Ca²⁺ channels decreased atrial myocyte atrial natriuretic peptide (ANP) release. The purpose of the present study was to address the effects of BDM in the regulation of ANP release. Experiments were performed in perfused beating rabbit atria. BDM accentuated atrial myocyte ANP release concomitantly with a decrease in atrial stroke volume and pulse pressure in a concentration-dependent manner. The BDM-induced activation of ANP release was attenuated by the treatment with nifedipine, an inhibitor of L-type Ca²⁺ channels. BDM further decreased atrial stroke volume and pulse pressure in the presence of nifedipine. Blockade of function of the sarcoplasmic reticulum with thapsigargin plus ryanodine slightly but not significantly attenuated the BDM-induced activation of ANP release. These data show that BDM is a potent stimulator for the ANP release and also suggest that the mechanism by which BDM activates atrial myocyte ANP release is related to inhibition of the L-type Ca²⁺ channel activity. The present finding also suggests that the effects of ANP released may be considered in an occasion of uncoupling by BDM of the excitation–contraction coupling of cardiomyocytes.     

慢性前列腺炎与细菌L型

本文用自行研制的883L型增菌培养基对51例次慢性前列腺炎患者的前列腺液作L型培养,结果检出L型细菌27例,占52.9％,经返祖和药物敏感性测定,证明本组L型细菌特性与其他来源的L型细菌基本相符,提示慢性前列腺炎的病因、病理机制可能与细菌L型的感染相关。