scholarly journals Similar Enhancement of BKCa Channel Function Despite Different Aerobic Exercise Frequency in Aging Cerebrovascular Myocytes

2016 ◽  
pp. 447-459 ◽  
Author(s):  
N. LI ◽  
B. LIU ◽  
S. XIANG ◽  
L. SHI
Keyword(s):  
Aerobic Exercise ◽  
Aerobic Exercise Training ◽  
Bkca Channel ◽  
Voltage Sensitivity ◽  
Open Probability ◽  
Exercise Frequency ◽  
Bkca Channels ◽  
Functional Changes ◽  
Young Rats ◽  
Training Frequency

Aerobic exercise showed beneficial influence on cardiovascular systems in aging, and mechanisms underlying vascular adaption remain unclear. Large-conductance Ca2+-activated K+ (BKCa) channels play critical roles in regulating cellular excitability and vascular tone. This study determined the effects of aerobic exercise on aging-associated functional changes in BKCa channels in cerebrovascular myocytes, Male Wistar rats aged 20-22 months were randomly assigned to sedentary (O-SED), low training frequency (O-EXL), and high training frequency group (O-EXH). Young rats were used as control. Compared to young rats, whole-cell BKCa current was decreased, and amplitude of spontaneous transient outward currents were reduced. The open probability and Ca2+/voltage sensitivity of single BKCa channel were declined in O-SED, accompanied with a reduction of tamoxifen-induced BKCa activation; the mean open time of BKCa channels was shortened whereas close time was prolonged. Aerobic exercise training markedly alleviated the aging-associated decline independent of training frequency. Exercise three times rather than five times weekly may be a time and cost-saving training volume required to offer beneficial effects to offset the functional declines of BKCa during aging.

scholarly journals CARDIAC STRUCTURAL AND FUNCTIONAL CHANGES AFTER SUSTAINED HIGH AEROBIC EXERCISE TRAINING STIMULUS

2015 ◽  
Vol 65 (10) ◽  
pp. A1508
Author(s):  
Satyam Sarma ◽  
William Dinsfriend ◽  
Erin Howden ◽  
William Cornwell ◽  
Kara Boyd ◽  
...  
Keyword(s):  
Exercise Training ◽  
Aerobic Exercise ◽  
Training Stimulus ◽  
Aerobic Exercise Training ◽  
Functional Changes

scholarly journals The β1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels

2004 ◽  
Vol 124 (4) ◽  
pp. 357-370 ◽  
Author(s):  
Lindsey Ciali Santarelli ◽  
Jianguo Chen ◽  
Stefan H. Heinemann ◽  
Toshinori Hoshi
Keyword(s):  
Bkca Channel ◽  
Open Probability ◽  
Bkca Channels ◽  
Additional Increase ◽  
Channel Activation ◽  
Α Subunit ◽  
Voltage Range ◽  
Virtual Absence ◽  
Methionine Residues ◽  
Oxidative Regulation

Oxidative stress may alter the functions of many proteins including the Slo1 large conductance calcium-activated potassium channel (BKCa). Previous results demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch-T), without the involvement of cysteine oxidation, increases the open probability and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) α subunits alone. Because native BKCa channel complexes may include the auxiliary subunit β1, we investigated whether β1 influences the oxidative regulation of hSlo1. Oxidation by Ch-T with β1 present shifted the half-activation voltage much further in the hyperpolarizing direction (−75 mV) as compared with that with α alone (−30 mV). This shift was eliminated in the presence of high [Ca2+]i, but the increase in open probability in the virtual absence of Ca2+ remained significant at physiologically relevant voltages. Furthermore, the slowing of channel deactivation after oxidation was even more dramatic in the presence of β1. Oxidation of cysteine and methionine residues within β1 was not involved in these potentiated effects because expression of mutant β1 subunits lacking cysteine or methionine residues produced results similar to those with wild-type β1. Unlike the results with α alone, oxidation by Ch-T caused a significant acceleration of channel activation only when β1 was present. The β1 M177 mutation disrupted normal channel activation and prevented the Ch-T–induced acceleration of activation. Overall, the functional effects of oxidation of the hSlo1 pore-forming α subunit are greatly amplified by the presence of β1, which leads to the additional increase in channel open probability and the slowing of deactivation. Furthermore, M177 within β1 is a critical structural determinant of channel activation and oxidative sensitivity. Together, the oxidized BKCa channel complex with β1 has a considerable chance of being open within the physiological voltage range even at low [Ca2+]i.

scholarly journals Revisiting the Large-Conductance Calcium-Activated Potassium (BKCa) Channels in the Pulmonary Circulation

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1629
Author(s):  
Divya Guntur ◽  
Horst Olschewski ◽  
Péter Enyedi ◽  
Réka Csáki ◽  
Andrea Olschewski ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Pulmonary Circulation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Free Calcium ◽  
Bkca Channel ◽  
Lung Pathology ◽  
Open Probability ◽  
Bkca Channels ◽  
Genes Encoding

Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell′s membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits. They are of vital significance due to their very high unitary conductance and hence their ability to rapidly cause extreme changes in the membrane potential. The pathophysiology of lung diseases in general and pulmonary hypertension, in particular, show the implication of either decreased expression and partial inactivation of BKCa channel and its subunits or mutations in the genes encoding different subunits of the channel. Signaling molecules, circulating humoral molecules, vasorelaxant agents, etc., have an influence on the open probability of the channel in pulmonary arterial vascular cells. BKCa channel is a possible therapeutic target, aimed to cause vasodilation in constricted or chronically stiffened vessels, as shown in various animal models. This review is a comprehensive collation of studies on BKCa channels in the pulmonary circulation under hypoxia (hypoxic pulmonary vasoconstriction; HPV), lung pathology, and fetal to neonatal transition, emphasising pharmacological interventions as viable therapeutic options.

scholarly journals The Effect of Aerobic Exercise Training Frequency on Arterial Stiffness in a Hyperglycemic State in Middle-Aged and Elderly Females

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3498
Author(s):  
Ryota Kobayashi ◽  
Kenji Asaki ◽  
Takeo Hashiguchi ◽  
Hideyuki Negoro
Keyword(s):  
Exercise Training ◽  
Arterial Stiffness ◽  
Aerobic Exercise ◽  
Exercise Group ◽  
Aerobic Exercise Training ◽  
Middle Aged ◽  
Healthy Elderly ◽  
Glucose Intake ◽  
Training Frequency ◽  
Rate Intensity

The frequency of aerobic exercise training in reducing the increase in arterial stiffness during acute hyperglycemia, a risk factor for cardiovascular disease, is unknown. The aim of the study was to determine the aerobic exercise training frequency on arterial stiffness in a hyperglycemic state in middle-aged and elderly females. Twenty healthy elderly people were randomly assigned to a two-times-a-week (T2, n = 10) and four-times-a-week (T4, n = 10) exercise group. All participants exercised for 35 min per session, which consisted of jogging exercises with a heart rate intensity of 65%. Brachial-ankle (ba), and heart-brachial (hb) pulse wave velocity (PWV) were measured before, 4 and 8 weeks after intervention; before the oral ingestion of 75-g of glucose; and 30, 60, and 90 min after ingestion. The baPWV before and 4 weeks after the intervention increased in both groups (p < 0.05), but only increased 8 weeks after intervention in the T2 group. hbPWV was unchanged before, 4 and 8 weeks after intervention in both groups. These findings show that frequent aerobic exercise suppresses the increase in arterial stiffness following glucose intake. The results of this study can be used to support the implementation of exercise programs for middle-aged and elderly patients.

scholarly journals PO-137 Epigenetic regulation of exercise-improved LTCC and BKCa channels function in hypertension mesenteric arteries

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Yanyan Zhang ◽  
Lijun Shi
Keyword(s):  
Protein Expression ◽  
Aerobic Exercise ◽  
Methylation Level ◽  
Gene Promoter ◽  
Mesenteric Arteries ◽  
Treadmill Running ◽  
Epigenetic Mechanism ◽  
Bkca Channel ◽  
Bkca Channels ◽  
Mrna And Protein Expression

Objective To investigate the epigenetic mechanism of the voltage-gated L-type Ca2+ channel (LTCC) and the large-conductance Ca2+-activated K+ channel (BKCa) function in mesenteric arterial myocytes improved by regular aerobic exercise in hypertension. Methods 12-week-old male SHR and WKY rats were randomly assigned to sedentary and exercise training groups, respectively. Exercise groups were performed a moderate-intensity treadmill running. After 8 weeks, patch clamp study, Ca2+ image, Western blot, qPCR, bisulfite sequencing PCR were used to detect the LTCC and BKCa channel currents, BKCa single channel gating properties, Ca2+ spark, mRNA and protein expression of LTCC α1c together with BKCa α and β1 subunits, DNA methylation level of α1c and β1 gene promoter region, miR-328 expression. In vitro experiment，miR-328 mimic and miR-328 inhibitor were transfected into cultured arterial myocytes to make miR-328 overexpressing or silencing, the mRNA and protein expression of α1c subunits were determined after 48 h transfection. Results 1) After 8 weeks of exercise, SBP in both exercise groups of WKY and SHR were significantly lower than that of their sedentary counterparts. 2) Exercise normalized the increased LTCC and BKCa current density of mesenteric arterial myocytes in SHR. 3) Exercise attenuated the increased single BKCa channel open Probability (Po) and the amplitude of Ca2+ spark in hypertension. 4) Exercise inhibited the upregulated mRNA and protein expression of BKCa β1 subunit in mesenteric arteries from SHR; β1 gene promoter was demethylation in hypertension, exercise increased the methylation level at β1 gene promoter of SHR. 5) The protein expression of LTCC α1c subunit was significantly increased in SHR, while decreased by exercise; the expression of miR-328 in mesenteric arteries was highly negative correlation with α1c subunit. 6) The miR-328 overexpression by transfecting miR-328 mimic decreased α1c subunit protein level significantly, while miR-328 inhibitor made α1c subunit a slight increase. Conclusions Regular aerobic exercise efficiently reduces blood pressure of SHR, enhances β1 gene promoter methylation, mediates miR-328 inhibiting the α1c expression at post-transcriptional level, which might be the epigenetic mechanism underlying exercise-improved LTCC and BKCa channels function in mesenteric arteries of hypertension.

scholarly journals Melatonin mediates vasodilation through both direct and indirect activation of BKCa channels

2017 ◽  
Vol 59 (3) ◽  
pp. 219-233 ◽  
Author(s):  
T Zhao ◽  
H Zhang ◽  
C Jin ◽  
F Qiu ◽  
Y Wu ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Relaxation Curve ◽  
Mesenteric Arteries ◽  
Voltage Sensitivity ◽  
Vascular Effects ◽  
Open Probability ◽  
Bkca Channels ◽  
Open Time ◽  
A Cell ◽  
Oxide Synthase

Melatonin, synthesized primarily by the pineal gland, is a neuroendocrine hormone with high membrane permeability. The vascular effects of melatonin, including vasoconstriction and vasodilation, have been demonstrated in numerous studies. However, the mechanisms underlying these effects are not fully understood. Large-conductance Ca2+-activated K+ (BKCa) channels are expressed broadly on smooth muscle cells and play an important role in vascular tone regulation. This study explored the mechanisms of myocyte BKCa channels and endothelial factors underlying the action of melatonin on the mesenteric arteries (MAs). Vascular contractility and patch-clamp studies were performed on myocytes of MAs from Wistar rats. Melatonin induced significant vasodilation on MAs. In the presence of Nω-nitro-l-arginine methyl ester (l-NAME), a potent endothelial oxide synthase (eNOS) inhibitor, melatonin elicited concentration-dependent relaxation, with lowered pIC50. The effect of melatonin was significantly attenuated in the presence of BKCa channel blocker iberiotoxin or MT1/MT2 receptor antagonist luzindole in both (+) l-NAME and (−) l-NAME groups. In the (+) l-NAME group, iberiotoxin caused a parallel rightward shift of the melatonin concentration–relaxation curve, with pIC50 lower than that of luzindole. Both inside-out and cell-attached patch-clamp recordings showed that melatonin significantly increased the open probability, mean open time and voltage sensitivity of BKCa channels. In a cell-attached patch-clamp configuration, the melatonin-induced enhancement of BKCa channel activity was significantly suppressed by luzindole. These findings indicate that in addition to the activation of eNOS, melatonin-induced vasorelaxation of MAs is partially attributable to its direct (passing through the cell membrane) and indirect (via MT1/MT2 receptors) activation of the BKCa channels on mesenteric arterial myocytes.

scholarly journals Modes of Operation of the BKCa Channel β2 Subunit

2007 ◽  
Vol 130 (1) ◽  
pp. 117-131 ◽  
Author(s):  
Nicoletta Savalli ◽  
Andrei Kondratiev ◽  
Sarah Buxton de Quintana ◽  
Ligia Toro ◽  
Riccardo Olcese
Keyword(s):  
Transmembrane Domain ◽  
K Channel ◽  
Bkca Channel ◽  
Kinetic Properties ◽  
Voltage Sensitivity ◽  
Bkca Channels ◽  
Channel Activation ◽  
Shaker Channels ◽  
Main Voltage ◽  
Inactivation Process

The β2 subunit of the large conductance Ca2+- and voltage-activated K+ channel (BKCa) modulates a number of channel functions, such as the apparent Ca2+/voltage sensitivity, pharmacological and kinetic properties of the channel. In addition, the N terminus of the β2 subunit acts as an inactivating particle that produces a relatively fast inactivation of the ionic conductance. Applying voltage clamp fluorometry to fluorescently labeled human BKCa channels (hSlo), we have investigated the mechanisms of operation of the β2 subunit. We found that the leftward shift on the voltage axis of channel activation curves (G(V)) produced by coexpression with β2 subunits is associated with a shift in the same direction of the fluorescence vs. voltage curves (F(V)), which are reporting the voltage dependence of the main voltage-sensing region of hSlo (S4-transmembrane domain). In addition, we investigated the inactivating mechanism of the β2 subunits by comparing its properties with the ones of the typical N-type inactivation process of Shaker channel. While fluorescence recordings from the inactivated Shaker channels revealed the immobilization of the S4 segments in the active conformation, we did not observe a similar feature in BKCa channels coexpressed with the β2 subunit. The experimental observations are consistent with the view that the β2 subunit of BKCa channels facilitates channel activation by changing the voltage sensor equilibrium and that the β2-induced inactivation process does not follow a typical N-type mechanism.

scholarly journals PPARG Pro12Ala Ala carriers exhibit greater improvements in peripheral insulin sensitivity in response to 12 weeks of aerobic exercise training

2019 ◽  
Vol 51 (6) ◽  
pp. 254-260
Author(s):  
Martin Bæk Blond ◽  
Theresia Maria Schnurr ◽  
Mads Rosenkilde ◽  
Jonas Salling Quist ◽  
Anne Sofie Gram ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Aerobic Exercise ◽  
Exercise Intervention ◽  
Aerobic Exercise Training ◽  
Exercise Frequency ◽  
Peripheral Insulin Sensitivity ◽  
Class 1 ◽  
Before And After ◽  
Exercise Energy Expenditure ◽  
Exercise Induced

The Ala allele of PPARG Pro12Ala ( rs1801282 ) is associated with greater improvements to the glucose metabolism in exercise studies, but whether this extends to peripheral insulin sensitivity is unknown. Our objective was to investigate the effect of PPARG Pro12Ala on exercise-induced changes in peripheral insulin sensitivity. A total of 124 (91 Pro homozygotes and 33 Ala carriers) previously physically inactive healthy young men and women with overweight or class 1 obesity who completed a 12 wk aerobic exercise intervention were included in the analysis. All participants underwent a hyperinsulinemic euglycemic clamp before and after the 12 wk intervention. The prescribed exercise frequency was 5–7 days/wk, and the exercise energy expenditure was 2,100 4,200 kcal/wk for men and 1,600 kcal/wk for women. Insulin sensitivity improved significantly in both genotype groups. However, Ala carriers had a 1.13-fold (95% confidence interval 1.01; 1.26, P = 0.032) greater improvement in insulin sensitivity from baseline compared with Pro homozygotes. Our data support that PPARG Pro12Ala modifies the effect of aerobic exercise on peripheral insulin sensitivity.

Age-Related Attenuation of Aerobic Exercise Training Adaptation in 24-Week Old Rats

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1916-P
Author(s):  
REBECCA L. SCALZO ◽  
GRAHAME F. EVANS ◽  
SARA E. HULL ◽  
LESLIE KNAUB ◽  
LORI A. WALKER ◽  
...  
Keyword(s):  
Exercise Training ◽  
Aerobic Exercise ◽  
Aerobic Exercise Training ◽  
Training Adaptation ◽  
Age Related ◽  
Old Rats
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