Marcie Berger

Intracellular acidosis differentially regulates KV channels in coronary and pulmonary vascular muscle

Decreases in intracellular pH (pHi) potently dilate coronary resistance arteries but constrict small pulmonary arteries. To define the ionic mechanisms of these responses, this study investigated whether acute decreases in pHi differentially regulate K+ currents in single vascular smooth muscle (VSM) cells isolated from rat coronary and pulmonary resistance arteries. In patch-clamp studies, whole cell K+ currents were elicited by 10-mV depolarizing steps between -60 and 0 mV in VSM cells obtained from 50- to 150-micrometers-OD arterial branches, and pHi was lowered by altering the NH4Cl gradient across the cell membrane. Progressively lowering pHi from calculated values of 7.0 to 6.7 and 6.4 increased the peak amplitude of K+ current in coronary VSM cells by 15 +/- 5 and 23 +/- 3% but reduced K+ current in pulmonary VSM cells by 18 +/- 3 and 21 +/- 3%, respectively. These changes were reversed by returning cells to the control pHi of 7.0 and were eliminated by dialyzing cells with pipette solution containing 50 mmol/l HEPES to buffer NH4Cl-induced changes in pHi. Pharmacological block of ATP-sensitive K+ channels and Ca2+-activated K+ channels by 1 micromol/l glibenclamide and 100 nmol/l iberiotoxin, respectively, did not prevent changes in K+ current levels induced by acidotic pHi. However, block of voltage-gated K+ channels by 3 mmol/l 4-aminopyridine abolished acidosis-induced changes in K+ current amplitudes in both VSM cell types. Interestingly, alpha-dendrotoxin (100 nmol/l), which blocks only select subtypes of voltage-gated K+ channels, abolished the acidosis-induced decrease in K+ current in pulmonary VSM cells but did not affect the acidosis-induced increase in K+ current observed in coronary VSM cells. These findings suggest that opposing, tissue-specific effects of pHi on distinct subtypes of voltage-gated K+ channels in coronary and pulmonary VSM membranes may differentially regulate vascular reactivity in these two circulations under conditions of acidotic stress.

Voltage and calcium-gated potassium channels: Functional expression and therapeutic potential in the vasculature

The dual expression of voltage-gated K+ (KV) channels and high conductance Ca2+-activated K+ (BKCa) channels in vascular smooth muscle membranes provides a fundamental mechanism for regulating the membrane potential and tone of resistance arteries. The distribution of these channels appears to differ between vascular regions, and diverse channel phenotypes resulting from molecular heterogeneity may mediate distinct patterns of excitability and contraction in specific vascular beds. Under physiological conditions, KV and BKCa channels appear to act in concert to regulate the level of contraction in the cerebral, coronary and pulmonary circulations, and thereby maintain blood flow to vital tissues. However, during cardiovascular pathologies, this profile of K+ channel function may be disrupted in vascular smooth muscle membranes, and unique disease-specific patterns of KV and BKCa channel expression may emerge. Under these conditions, drug therapies designed to normalize K+ channel expression or target overexpressed channels in arterial smooth muscle membranes may have potential value for the treatment of vascular diseases.

Pacemaker Quantified Physical Activity Predicts All-Cause Mortality.

There is growing recognition that physical inactivity in the general population is an important risk factor for cardiovascular disease and death [(1–3)][1]. To date, there are limited data as to the predictive value of physical activity in individuals with pacemakers and preserved left ventricular

CLINICAL OUTCOMES AFTER CARDIAC MRI SCANS OF NON-MRI-SAFE CARDIAC IMPLANTABLE ELECTRONIC DEVICES

Few studies have been published regarding the safety or feasibility of MRIs in patients with cardiac implantable electronic devices (CIEDs), and most have excluded patients requiring cardiac MRIs. This study evaluated the immediate and 6-month effects on device parameters in patients who underwent

WHAT CAME FIRST, THE CHICKEN OR THE EGG? HIGH DEGREE AV BLOCK AND TAKOTSUBO'S CARDIOMYOPATHY

Takostubos cardiomyopathy is a transient left ventricular(LV) dysfunction that usually follows an acute stressful event like an acute medical illness or other forms of emotional or physical stress. There are few case reports of this cardiomyopathy associated with high degree AV block reported in

Induction of Ca2+ -Activated K+ Channel Expression during Systemic Hypertension: Protection against Pathological Vasoconstriction

During the past 15 years, patch-clamp studies have characterized a diverse population of K+ channel types in vascular smooth muscle cells. Prominent among these is the high-conductance, Ca2+ -activated K+ channel (BKCa channel), which appears to be ubiquitously expressed in arterial smooth muscle membranes. The BKCa channel in some vascular beds may act together with other K+ channel types to set the level of resting membrane potential in the arterial smooth muscle cells. During vascular excitation, the further activation of BKCa channels may provide a powerful pathway to hyperpolarize the arterial smooth muscle cells, thereby limiting voltage-gated Ca2+ influx and buffering vasoconstriction in small arteries and resistance vessels. Thus, under physiological conditions, the BKCa channel acts as a homeostatic mechanism to counteract arterial constriction and maintain blood flow to critical organs and tissues.