Distal colonic K(+) excretion is determined by the balance of K(+) absorption and K(+) secretion of the enterocytes. K(+) secretion occurs via active basolateral K(+) uptake mostly via the NKCC1 co-transporter followed by K(+) exit via a luminal K(+) channel. The specific focus here is directed towards the luminal secretory K(+) channel (1). Several recent observations highlight the pivotal rol...

We examined the actions of ethanol on the single channel properties of large conductance Ca2+-activated K+ (BK) channels isolated from skeletal muscle T-tubule membranes and incorporated into planar lipid bilayer membranes. We have taken advantage of this preparation, because it lacks most elements of cellular complexity, including cytoplasmic constituents and complex membrane lipid composition...

Our recent study has revealed that 12,14-dichlorodehydroabietic acid (diCl-DHAA), which is synthetically derived from a natural product, abietic acid, is a potent opener of large conductance Ca -activated K (BK) channel. Here, we examined, by using a channel expression system in human embryonic kidney 293 cells, the mechanisms underlying the BK channel opening action of diCl-DHAA and which subu...

Large conductance, Ca(2+)-activated K(+) (BK) channels represent an important pathway for the outward flux of K(+) ions from the intracellular compartment in response to membrane depolarization, and/or an elevation in cytosolic free [Ca(2+)]. They are functionally expressed in a range of mammalian tissues (e.g., nerve and smooth muscles), where they can either enhance or dampen membrane excitab...

Estrogens have an important role in regulating detrusor smooth muscle (DSM) function. However, the underlying molecular and cellular mechanisms by which estrogens control human DSM excitability and contractility are not well known. Here, we used human DSM specimens from open bladder surgeries on 27 patients to elucidate the mechanism by which 17β-estradiol regulates large conductance voltage- a...

Petkov GV. Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology. Am J Physiol Regul Integr Comp Physiol 307: R571– R584, 2014. First published July 2, 2014; doi:10.1152/ajpregu.00142.2014.—The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the uri...

A major challenge is to understand maladaptive changes in ion channels that sets neurons on a course towards epilepsy development. Voltage- and calcium-activated K+ (BK) channels contribute to early spike timing in neurons, and studies indicate that the BK channel plays a pathological role in increasing excitability early after a seizure. Here, we have investigated changes in BK channels and th...

Bile acids have been reported to produce relaxation of smooth muscle both in vitro and in vivo. The cellular mechanisms underlying bile acid-induced relaxation are largely unknown. Here we demonstrate, using patch-clamp techniques, that natural bile acids and synthetic analogues reversibly increase BK(Ca) channel activity in rabbit mesenteric artery smooth muscle cells. In excised inside-out pa...

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca release events (Ca -sparks), trigger the activation of large-conductance Ca -activated K (BK)-channels which hyperpolarize and relax vascular smooth muscle cells, th...

AIMS Tungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent K(+) (BK) channel is a key element in the control of arterial tone, our aim was to evaluate whether BK channel modulation by tungstate can contribute to its ant...