ABSTRACT
BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel's activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.
ABSTRACT
BACKGROUND: It is difficult to simulate the abnormal myocardial strain patterns caused by ischemic coronary artery disease (CAD) which are a precursor to heart failure (HF) within an animal model. Simulation of these strain changes could contribute to better understanding of the early formative stages of HF. This is especially important in investigating the poorly understood pathogenesis of heart failure with preserved ejection fraction (HFpEF). Here, we discuss delivery of high intensity focused ultrasound (HIFU) in a murine model to alter left ventricular (LV) regional longitudinal strain (RLS), and use of speckle tracking echocardiography to detect these changes. METHODS: HIFU pulses (pressure amplitude 1.7 MPa) were generated by amplifying a sinusoidal waveform from a function generator into a piezoelectric transducer. These pulses were then directed extracorporeally towards the anterior LV surface of C57BI6 mice during three time periods (early, mid, and late diastole). Speckle tracking echocardiography was then used to quantify changes in RLS within six segments of the LV. RESULTS: We observed an increase in LV RLS with acoustic augmentation during all three time periods. This augmentation was most prominent near the anterior apical region in early diastole and near the posterior basilar region during late diastole. CONCLUSIONS: Our findings demonstrate the application of HIFU to non-invasively induce changes in RLS within a murine model. Our results also reflect the capability of speckle tracking echocardiography to analyze and quantify these changes. These findings represent the first demonstration of ultrasound-induced augmentation in LV RLS within a small animal model.
ABSTRACT
We studied the spreading of a thin film of hexadecane oil on a hydrophobic polystyrene surface, which is partially covered with tiny water droplets. In spite of the fact that the spreading coefficient of hexadecane is slightly negative on water, the oil actually spreads faster on the droplet covered polystyrene than on the pure substrate. The observed effect is partly due to the geometric factors that lead to greater reduction of oil-substrate interfacial energy in comparison to the increase of oil-vapor surface energy. However, it is more important to consider the reduction of the resistance to fluid motion in the presence of condensed droplets. We provide an explanation of the phenomenon by drawing an analogy to the spreading on a rough surface, in which each water drop nucleates and re-initiates the spreading process. The phenomenon is therefore an approximate 2D version of liquid invasion through porous media.
