Pflügers Archiv

Using the inside-out patch-clamp technique, large-conductance Ca2+-activated K+ channel (BKCa) currents were recorded from coronary artery smooth muscle cells. Cytochalasin D, an actin filament disrupter, increased channel activity (NP o, where N is the number of channels and P o the open probability), and this increase was reversed by phalloidin, an actin filament stabilizer. NP o was also increased by colchicine, a microtubule disrupter, and decreased by taxol, a microtubule stabilizer. With the stepwise increase of negative pressure in the patch pipettes, the activity of BKCa gradually increased: the maximum effect (527% increase in NP o) was achieved at −40 cmH2O and the half-maximum effect at −25 cmH2O. The increase in NP o in response to negative pressure was abolished by phalloidin but not by taxol. These results imply that both actin filaments and microtubules inhibit the opening of BKCa in coronary artery smooth muscle cells, but that only actin filaments are involved in the stretch sensitivity of BKCa.

In human latissimus dorsi muscle a preponderance of type 2b fibres in the first fascicle layer and of type 1 fibres in the second layer was found. NADH-dehydrogenase (NADH) andα-glycero-phosphate dehydrogenase (GPDH) which were measured histophotometrically in type 1, 2a, and 2b fibres showed either extreme or only partial overlapping regarding the activity of metabolic enzymes. In different fascicle layers the average activity of both enzymes did not differ significantly among the fibres of the same type, neither did the NADH and GPDH activity of type 2a and 2b.

In experiments in pentobarbital anaesthetized cats the CO2 tensions in arterial blood and in cerebrospinal fluid (CSF) were measured with and without ventriculo-cisternal perfusion at different levels of anaesthesia. It was found that at arterial $$P_{{\text{CO}}_2 }$$ values from 30–60 mm Hg, the linear relationship between the CSF-arterial $$P_{{\text{CO}}_2 }$$ difference and the arterial $$P_{{\text{CO}}_2 }$$ was influenced by the depth of anaesthesia. However, at a “normal” $$Pa_{{\text{CO}}_2 }$$ of about 35 mm Hg the CSF-arterial $$P_{{\text{CO}}_2 }$$ difference was about the same at different levels of anaesthesia. During ventriculo-cisternal perfusion the CSF-arterial $$P_{{\text{CO}}_2 }$$ difference was found to be about 3 mm Hg higher than in the unperfused cat.

Epigenetics refers to phenotypic changes caused by mechanisms that are unrelated to changes in the underlying DNA sequence, most notably chromatin remodeling driven by histone modifications, and DNA methylation. Such variation is transmitted by cell division, but generally not passed on through the germ line. An increasing body of evidence supports a role for epigenetic changes in the etiology of aging and its associated disease sequelae. Here, we review the role of epigenetics in aging and longevity with a focus on DNA methylation. Increased understanding of those aging-related processes that are driven by epigenetic mechanisms will allow for the development of novel epigenetic-based diagnostic, preventive, and therapeutic strategies for age-related diseases.