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Sperm of salmonid fishes are quiescent in the presence of millimolar concentrations of extracellular K+, but motility initiation occurs when sperm are suspended in K+-free medium. In this study, glycerol (CH2OHCHOHCH2OH) treatment of intact sperm in the presence of K+ induced the initiation of motility even though a large amount of K+ was present. Another organic alcohol, erythritol (CH2OH(CHOH)2CH2OH), had a similar effect, but ethylene glycol (CH2OHCH2OH) did not initiate sperm motility. Furthermore, this glycerol-treated sperm showed motility without subsequent addition of ATP and cAMP. CCCP, an uncoupler of the mitochondrial electron-transport chain involved in ATP synthesis, suppressed motility of glycerol-treated sperm, suggesting that ATP synthesis is required for dynein to slide microtubules in glycerol-treated sperm. The amount of intracellular cAMP ([cAMP]i) in glycerol-treated sperm did not increase on motility activation, but a protein kinase A (PKA) inhibitor, H-89, inhibited glycerol-treated sperm motility. In addition, phosphorylation of protein associated with motility initiation also occurred in glycerol-treated sperm, suggesting that the glycerol treatment induces activation of PKA without an increase in [cAMP]i. Taken together, it can be concluded that organic alcohol, glycerol and erythritol induce phosphorylation for motility initiation, bypassing the increase in [cAMP]i as a result of a decrease in extracellular K+ concentration.

Background: The left ventricular functional recovery by beta-blocker therapy is now attributed to time-dependent biologic effects on cardiomyocytes., Methods and Results: To elucidate the cellular mechanism of these biologic effects, we treated 9 patients with dilated cardiomyopathy for 4 months with beta-blockers and examined the gene expressions linked to an improvement of left ventricular ejection fraction (EF). Gene expressions of the biopsied right ventricular endomyocardium were assessed by real-time reverse transcription-polymerase chain reaction. A decrease in beta-myosin heavy chain (1.23+/-0.49 versus 0.86+/-0.45, P<.05) was observed 4 months after the administration of beta-blockers. The expression levels of both sarcoplasmic reticulum Ca(2+) ATPase (SERCA) (0.80+/-0.28 versus 1.39+/-0.44, P<.01) and phospholamban (PLB) (0.49+/-0.08 versus 0.88+/-0.34, P<.05) increased, whereas the expression levels of Na(+)-Ca(2+) exchanger (NCX), beta-adrenoreceptor kinase 1, and ryanodine receptor 2 were unchanged. The SERCA/NCX ratio (0.68+/-0.14 versus 0.96+/-0.33, P<.05) also increased. The increase in SERCA mRNA expression correlated with the degree of changes in EF (%deltaEF) (r=0.679, P<.05), and none of changes in these genes expression correlated with changes in the plasma brain natriuretic peptide concentration., Conclusions: The functional recovery resulting from beta-blockers may be associated with the restoration of the unfavorable gene expression that controls Ca(2+) handlings in the failing heart.