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At least 19 recordsLinked to original sources
PubMed2005

Diabetes and insulin secretion: the ATP-sensitive K+ channel (K ATP) connection.

The ATP-sensitive K+ channel (K ATP channel) senses metabolic changes in the pancreatic beta-cell, thereby coupling metabolism to electrical activity and ultimately to insulin secretion. When K ATP channels open, beta-cells hyperpolarize and insulin secretion is suppressed. The prediction that K ATP channel "overactivity" should cause a diabetic state due to undersecretion of insulin has been dramatically borne out by recent genetic studies implicating "activating" mutations in the Kir6.2 subunit of K ATP channel as causal in human diabetes. This article summarizes the emerging picture of K ATP channel as a major cause of neonatal diabetes and of a polymorphism in K ATP channel (E23K) as a type 2 diabetes risk factor. The degree of K ATP channel "overactivity" correlates with the severity of the diabetic phenotype. At one end of the spectrum, polymorphisms that result in a modest increase in K ATP channel activity represent a risk factor for development of late-onset diabetes. At the other end, severe "activating" mutations underlie syndromic neonatal diabetes, with multiple organ involvement and complete failure of glucose-dependent insulin secretion, reflecting K ATP channel "overactivity" in both pancreatic and extrapancreatic tissues.

Adenosine Triphosphate↗
PubMed1996

Immunolocalization of an inwardly rectifying K+ channel, K(AB)-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia.

Immunolocalization of K(AB)-2 (Kir4.1), an inwardly rectifying K+ channel with a putative ATP-binding domain, was examined in rat kidney where expression of K(AB)-2 mRNA was previously shown. Anti-K(AB)-2 antibody was raised in rabbit and then affinity-purified. An immunohistochemical study revealed that K(AB)-2 immunoreactivity was detected specifically in the basolateral membrane of distal tubular epithelia. Therefore, K(AB)-2 is the first K+ channel shown to be localized in the basolateral membrane of renal epithelia. The finding suggests that K(AB)-2 may contribute to supplying K+ to the Na(+)-K+ pump, which is abundant in the basolateral membrane of distal tubular epithelia, as well as to maintenance of the deep negative membrane potential of these cells.

Amino Acid Sequence↗
PubMed1999

[Pre- and postsynaptic action of the ATP-dependent K+-channel-(K+ATP)-opener pinacidil in rabbit pulmonary artery].

Low frequency (2 Hz) of electrical depolarisation induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3x10(-5)M and corticosterone, 5x10(-5)M), with parallel measurements of post-junctional contractile responses. The K+ATP-channel opener pinacidil (10(-6)-10(-4)M), slightly potentiated the nerve-evoked release of [3H]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10(-4)M) increased the ratio of [3H]NA release from 0.99 +/- 0.02 to 1.28 +/- 0.05 (P < 0.0005). On the other hand, pinacidil inhibited the nerve-evoked contractions in a concentration-dependent manner. 10(-4)M caused nearly 70% inhibition of contractile response. The pre- and post-junctional effects of pinacidil were studied under the following experimental conditions: 1) exogenously applied 1-NA; 2) excess K+; 3) 'L-type' Ca(2+)-channel activation (BAY K 8644); K(+)-channel inhibition (4-AP); and 5) Na(+)-pump inhibition/reactivation. Pinacidil (10(-4)M) retained its marginal NA-release stimulatory effect in all cases. However, pinacidil inhibited the contraction of smooth muscle, although to a different extent, in all of the experimental conditions used in our study.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2003

Is ATP-sensitive K+ channel (K+ATP) recruitment a common mechanism for ECG-ST segment depression and elevation?

ATP sensitive (K(+)(ATP)) potassium cardiac channels are recruited when ATP levels are low as in ischemic injury and acute trauma. Such activation results in ECG-ST elevation and cardiac arrhythmias. K(+)(ATP) channel recruitment may be blocked by the sulfonylurea glibenclamide, permitting a wide variety of animal experimentation designed to test the genesis of ECG-ST segment elevations and depressions in diverse conditions including digitalis effect, acute arterial occlusion, tachycardias, and acute pericarditis. A specific series of animal experiments designed to test this hypothesis is proposed. Clinical implications are discussed.

Action Potentials↗
PubMed1999

A transmembrane domain of the sulfonylurea receptor mediates activation of ATP-sensitive K(+) channels by K(+) channel openers.

ATP-sensitive K(+) (K(ATP)) channels are a complex of an ATP-binding cassette transporter, the sulfonylurea receptor (SUR), and an inward rectifier K(+) channel subunit, Kir6.2. The diverse pharmacological responsiveness of K(ATP) channels from various tissues are thought to arise from distinct SUR isoforms. Thus, when assembled with Kir6. 2, the pancreatic beta cell isoform SUR1 is activated by the hyperglycemic drug diazoxide but not by hypotensive drugs like cromakalim, whereas the cardiac muscle isoform SUR2A is activated by cromakalim and not by diazoxide. We exploited these differences between SUR1 and SUR2A to pursue a chimeric approach designed to identify the structural determinants of SUR involved in the pharmacological activation of K(ATP) channels. Wild-type and chimeric SUR were coexpressed with Kir6.2 in Xenopus oocytes, and we studied the resulting channels with the patch-clamp technique in the excised inside-out configuration. The third transmembrane domain of SUR is found to be an important determinant of the response to cromakalim, which possibly harbors at least part of its binding site. Contrary to expectations, diazoxide sensitivity could not be linked specifically to the carboxyl-terminal end (nucleotide-binding domain 2) of SUR but appeared to involve complex allosteric interactions between transmembrane and nucleotide-binding domains. In addition to providing direct evidence for the structure-function relationship governing K(ATP) channel activation by potassium channel-opening drugs, a family of drugs of the highest therapeutic interest, these findings delineate the determinants of ligand specificity within the modular ATP-binding cassette-transporter architecture of SUR.

ATP-Binding Cassette Transporters↗
PubMed2001

Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi-K channel.

K+ secretion by the cortical collecting duct (CCD) is stimulated at high flow rates. Patch-clamp analysis has identified a small-conductance secretory K+ (SK) and a high-conductance Ca(2+)-activated K+ (maxi-K) channel in the apical membrane of the CCD. The SK channel, encoded by ROMK, is believed to mediate baseline K+ secretion. The role of the stretch- and Ca2+-activated maxi-K channel is still uncertain. The purpose of this study was to identify the K+ channel mediating flow-dependent K+ secretion in the CCD. Segments isolated from New Zealand White rabbits were microperfused in the absence and presence of luminal tetraethylammonium (TEA) or charybdotoxin, both inhibitors of maxi-K but not SK channels, or apamin, an inhibitor of small-conductance maxi-K+ channels. Net K+ secretion and Na+ absorption were measured at varying flow rates. In the absence of TEA, net K+ secretion increased from 8.3 +/- 1.0 to 23.4 +/- 4.7 pmol. min(-1). mm(-1) (P < 0.03) as the tubular flow rate was increased from 0.5 to 6 nl. min(-1). mm(-1). Flow stimulation of net K+ secretion was blocked by luminal TEA (8.2 +/- 1.2 vs. 9.9 +/- 2.7 pmol. min(-1). mm(-1) at 0.6 and 6 nl. min(-1). mm(-1) flow rates, respectively) or charybdotoxin (6.8 +/- 1.6 vs. 8.3 +/- 1.6 pmol. min(-1). mm(-1) at 1 and 4 nl. min(-1). mm(-1) flow rates, respectively) but not by apamin. These results suggest that flow-dependent K+ secretion is mediated by a maxi-K channel, whereas baseline K+ secretion occurs through a TEA- and charybdotoxin-insensitive SK (ROMK) channel.

Animals↗
PubMed1994

Structural determinant for assembly of mammalian K+ channels.

K+ channel function is regulated through the assembly of channel subunit isoforms into either homo- or heterotetrameric structures each characterized by distinct pharmacologic and kinetic properties. In studying the molecular basis of subunit association in mammalian Shaker-like K+ channels, we constructed deletion mutants of the inactivating K+ channel hKv1.4 alone and in tandem with hKv1.5 and examined the functional properties electrophysiologically in Xenopus oocytes. Deletion of 255 amino acids in the amino-terminal domain of hKv1.4 prevented the formation of hybrid channels within the subfamily but had no effect on homomultimerization or voltage-dependent gating. The amino-terminal deletion mutant of Kv2.1, a noninactivating K+ channel from a distantly related subfamily also forms functional homomultimeric channels. Although members of different K+ channel subfamilies do not coassemble, coexpression of the amino-terminal deletion mutants of hKv1.4 and Kv2.1 resulted in the formation of functional hybrid channels. These results demonstrate that the amino-terminal region of mammalian K+ channels subserves two functions. It provides a recognition site necessary for hetero- but not homomultimeric channel assembly within a subfamily and prevents coassembly between subfamilies.

Animals↗
PubMed1999

Molecular diversity of K+ channels.

K+ channel principal subunits are by far the largest and most diverse of the ion channels. This diversity originates partly from the large number of genes coding for K+ channel principal subunits, but also from other processes such as alternative splicing, generating multiple mRNA transcripts from a single gene, heteromeric assembly of different principal subunits, as well as possible RNA editing and posttranslational modifications. In this chapter, we attempt to give an overview (mostly in tabular format) of the different genes coding for K+ channel principal and accessory subunits and their genealogical relationships. We discuss the possible correlation of different principal subunits with native K+ channels, the biophysical and pharmacological properties of channels formed when principal subunits are expressed in heterologous expression systems, and their patterns of tissue expression. In addition, we devote a section to describing how diversity of K+ channels can be conferred by heteromultimer formation, accessory subunits, alternative splicing, RNA editing and posttranslational modifications. We trust that this collection of facts will be of use to those attempting to compare the properties of new subunits to the properties of others already known or to those interested in a comparison between native channels and cloned candidates.

Alternative Splicing↗
PubMed2000

Enhancement of Na(+) uptake currents, time-dependent inward-rectifying K(+) channel currents, and K(+) channel transcripts by K(+) starvation in wheat root cells.

Excessive low-affinity Na(+) uptake is toxic to the growth of glycophytic plants. Recently, several reports have suggested that the interaction between K(+) and Na(+) uptake might represent a key factor in determining the Na(+) tolerance of plants. We investigated the effects of K(+) starvation on Na(+) and K(+) uptake mechanisms in the plasma membrane of wheat (Triticum aestivum L.) root cortex cells using the patch-clamp technique. Unexpectedly, K(+) starvation of wheat seedlings was found to enhance the magnitude and frequency of occurrence of time-dependent inward-rectifying K(+) channel currents (I(K)(+)(in)). We examined whether the transcription of a wheat root K(+)(in) channel gene is induced by K(+) starvation. A cDNA coding for a wheat root K(+) channel homolog, TaAKT1 (accession no. AF207745), was isolated. TaAKT1 mRNA levels were up-regulated in roots in response to withdrawal of K(+) from the growth medium. Furthermore, K(+) starvation caused an enhancement of instantaneous Na(+) currents (I(Na)(+)). Electrophysiological analyses suggested that I(K)(+)(in) and I(Na)(+) are not mediated by the same transport protein based on: (a) different activation curves, (b) different time dependencies, (c) different sensitivities to external Ca(2+), and (d) different cation selectivities. These data implicate a role for I(Na)(+) in Na(+) uptake and stress during K(+) starvation, and indicate that K(+)(in) channels may contribute to K(+)-starvation-induced K(+) uptake in wheat roots.

Amino Acid Sequence↗
PubMed2006

Crystallographic study of the tetrabutylammonium block to the KcsA K+ channel.

K(+) channels play essential roles in regulating membrane excitability of many diverse cell types by selectively conducting K(+) ions through their pores. Many diverse molecules can plug the pore and modulate the K(+) current. Quaternary ammonium (QA) ions are a class of pore blockers that have been used for decades by biophysicists to probe the pore, leading to important insights into the structure-function relation of K(+) channels. However, many key aspects of the QA-blocking mechanisms remain unclear to date, and understanding these questions requires high resolution structural information. Here, we address the question of whether intracellular QA blockade causes conformational changes of the K(+) channel selectivity filter. We have solved the structures of the KcsA K(+) channel in complex with tetrabutylammonium (TBA) and tetrabutylantimony (TBSb) under various ionic conditions. Our results demonstrate that binding of TBA or TBSb causes no significant change in the KcsA structure at high concentrations of permeant ions. We did observe the expected conformational change of the filter at low concentration of K(+), but this change appears to be independent of TBA or TBSb blockade.

Crystallography, X-Ray↗
PubMed2003

Fatty acid-sensitive two-pore domain K+ channels.

K(+) channels that are activated by free fatty acids (here called K(FA) channels) are found throughout the CNS and in some peripheral tissues. In addition to free fatty acids, membrane stretch (cell swelling), changes in intracellular pH and volatile anaesthetic agents also activate K(FA) channels. Neurotransmitters that bind to G(s)-protein-coupled receptors inhibit K(FA) current via cAMP-mediated phosphorylation. K(FA) channels are native members of the TREK-TRAAK family, which belongs to the tandem-pore class of K(+) (K(2P)) channels. The unique properties of K(FA) channels indicate that they are well suited to sensing various types of stress that occur in the cell.

Animals↗
PubMed1995

Molecular determinants of ion conduction and inactivation in K+ channels.

K+ channel-forming proteins can be grouped into three families that differ by the number of potential membrane-spanning segments. The largest of these families is composed of tetrameric channels with subunits containing six putative membrane-spanning segments (S1-S6). Inward rectifiers comprise a second family of K+ channels with subunits having two transmembrane domains (M1, M2). Monomers in the third family are proteins containing only one membrane-spanning segment, and they give origin to minK+ channels. Joining together segments S5 and S6 in the case of voltage-gated K+ channels and M1 and M2 in inward rectifiers, there is a highly conserved region with a hairpin shape called the H5 or P region. The P region, the loop connecting the S4 and S5 domains and the S6 transmembrane segment in Shaker-type K+ channels and the COOH-terminal in inward rectifiers, appears to play crucial roles in ion conduction. In Shaker K+ channels the NH2-terminal has been identified as responsible for fast inactivation (N-type inactivation). If the fast-inactivation gate is removed, a slower inactivation process persists, and its rate can be altered by mutations of amino acid residues forming part of the region in the neighborhood of the COOH-terminal (C-type inactivation). In this review we discuss the strategies followed to identify the different structures of K+ channels involved in ion conduction and inactivation processes and how they interplay.

Amino Acid Sequence↗
PubMed1996

Dynamic changes of mechanically activated channels and K+ channels at injury site of peripheral nerve in rat.

Ectopic ion channels developed locally at the injury site after nerve damage by light ligation around common sciatic nerve of the rats. Different channel types have different processes of formation, accumulation and degeneration. During the first three days after injury, mechanically activated channels that are modulated by CA++ channel activities first appeared. As the nerve fibers begin to be excited by TEA, a blocker of K+ channels, suggesting that the accumulation of K+ channels, the responsibility of mechanically activated channels was declining. Onset of K+ channels was from the 3rd postoperative day and lasted up to the fiftieth day. This time course of K+ channel development was closely related to allodynia and hyperalgesia of neuropathic animal behaviour. The results suggest that chronic contraction injury induces a dynamic change in the ectopic mechanically activated channels and K+ channels at the injury site of nerve and there is an interchange in the development time courses of the mechanically activated channels and K+ channels.

Action Potentials↗
PubMed2000

Dynamic control of deactivation gating by a soluble amino-terminal domain in HERG K(+) channels.

K(+) channels encoded by the human ether-à-go-go-related gene (HERG) are distinguished from most other voltage-gated K(+) channels by an unusually slow deactivation process that enables cardiac I(Kr), the corresponding current in ventricular cells, to contribute to the repolarization of the action potential. When the first 16 amino acids are deleted from the amino terminus of HERG, the deactivation rate is much faster (Wang, J., M.C. Trudeau, A.M. Zappia, and G.A. Robertson. 1998. J. Gen. Physiol. 112:637-647). In this study, we determined whether the first 16 amino acids comprise a functional domain capable of slowing deactivation. We also tested whether this "deactivation subdomain" slows deactivation directly by affecting channel open times or indirectly by a blocking mechanism. Using inside-out macropatches excised from Xenopus oocytes, we found that a peptide corresponding to the first 16 amino acids of HERG is sufficient to reconstitute slow deactivation to channels lacking the amino terminus. The peptide acts as a soluble domain in a rapid and readily reversible manner, reflecting a more dynamic regulation of deactivation than the slow modification observed in a previous study with a larger amino-terminal peptide fragment (Morais Cabral, J.H., A. Lee, S.L. Cohen, B.T. Chait, M. Li, and R. Mackinnon. 1998. Cell. 95:649-655). The slowing of deactivation by the peptide occurs in a dose-dependent manner, with a Hill coefficient that implies the cooperative action of at least three peptides per channel. Unlike internal TEA, which slows deactivation indirectly by blocking the channels, the peptide does not reduce current amplitude. Nor does the amino terminus interfere with the blocking effect of TEA, indicating that the amino terminus binding site is spatially distinct from the TEA binding site. Analysis of the single channel activity in cell-attached patches shows that the amino terminus significantly increases channel mean open time with no alteration of the mean closed time or the addition of nonconducting states expected from a pore block mechanism. We propose that the four amino-terminal deactivation subdomains of the tetrameric channel interact with binding sites uncovered by channel opening to specifically stabilize the open state and thus slow channel closing.

Animals↗
PubMed1997

Effects of K+ channel blockers on K+ channels, membrane potential, and aldosterone secretion in rat adrenal zona glomerulosa cells.

The hypothesis that angiotensin II (ANG II)-induced aldosterone secretion is mediated through inhibition of plasma membrane K+ channels was examined by measuring the effects of K+ channel blockers on K+ currents, membrane potential, and aldosterone secretion in rat adrenal glomerulosa cells. Effective K+ channel blockers were identified and studied using patch clamp methods on isolated glomerulosa cells in cell culture. Extracellular Cs+ (2-20 mm) caused a voltage-dependent inhibition of macroscopic K+ currents, exhibiting an apparent Kd of 2 mM for blockade of K+ current at membrane potentials near the K+ equilibrium potential. Outward K+ current opposed the Cs+ block, imparting a steep voltage dependence to this block. In single channel studies Cs blocked inward, but not outward, unitary currents through ANG II-regulated weakly voltage-dependent K+ channels, which are thought to control resting membrane potential. Cs+ reversibly depolarized the resting membrane potential at concentrations greater than or equal to the apparent Kd for K+ conductance inhibition (> or =2 mM). Depolarization consisted of a slow, maintained phase proportional to Cs+ concentration superimposed with 2- to 5-mV transient depolarizing events. Cs+ induced a Ca2+-dependent stimulation of aldosterone secretion in acutely dissociated cells, exhibiting an EC50 of approximately 3 mM. Maximal Cs+-induced secretion was quantitatively similar to 1 nM ANG II- or 8 mM K+-induced secretion. Cs+-induced secretion was not additive with that of ANG II. K+ channel blockers that did not inhibit weakly voltage-dependent K+ channels at rest (quinidine, apamin, and charybdotoxin) did not cause depolarization or stimulate aldosterone secretion. Furthermore, charybdotoxin did not significantly affect ANG II-induced aldosterone secretion, indicating that Ca2+-dependent maxi-K+ channels did not contribute to the control of aldosterone secretion in acutely dissociated cells. These data strongly support involvement of weakly voltage-dependent K+ channels in ANG II-induced aldosterone secretion, but also implicate roles for other channel classes in controlling membrane potential during ANG II-induced aldosterone secretion.

Aldosterone↗
PubMed2001

Energetics of ion conduction through the K+ channel.

K+ channels are transmembrane proteins that are essential for the transmission of nerve impulses. The ability of these proteins to conduct K+ ions at levels near the limit of diffusion is traditionally described in terms of concerted mechanisms in which ion-channel attraction and ion-ion repulsion have compensating effects, as several ions are moving simultaneously in single file through the narrow pore. The efficiency of such a mechanism, however, relies on a delicate energy balance-the strong ion-channel attraction must be perfectly counterbalanced by the electrostatic ion-ion repulsion. To elucidate the mechanism of ion conduction at the atomic level, we performed molecular dynamics free energy simulations on the basis of the X-ray structure of the KcsA K+ channel. Here we find that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the 'knock-on' mechanism proposed by Hodgkin and Keynes in 1955. The largest free energy barrier is on the order of 2-3 kcal mol-1, implying that the process of ion conduction is limited by diffusion. Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective.

Bacterial Proteins↗
PubMed2005

O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells.

Hypoxic inhibition of K+ channels provides a link between low O2 and cell function, and in glossopharyngeal neurons hypoxic inhibition of a TWIK-related halothane-inhibitable K+ channel-1 (THIK-1)-like background K+ channel regulates neuronal function. In the present study, we examined directly the O2 sensitivity of recombinant THIK-1 channels, expressed in human embryonic kidney (HE293) cells. THIK-1 expression conferred a moderately outwardly rectifying halothane-inhibited and arachidonic acid-potentiated K+ current and invoked a strongly hyperpolarized resting membrane potential. Endogenous K+ currents in untransfected cells were unaffected by either agent. Hypoxia (P(O2), 20 mmHg) reversibly inhibited THIK-1 currents and caused membrane depolarization, effects that were occluded by halothane. Neither the mitochondrial complex I inhibitors rotenone, myxothiazol and sodium cyanide, nor the NADPH oxidase inhibitors diphenylene iodonium and phenylarsine oxide, were effective in inhibiting the O2-sensitivity of THIK-1. Thus, hypoxic inhibition of THIK-1 occurs by a mechanism dissimilar to that which regulates the activity of other members of the background K+ channel family. Given the O2 sensitivity of THIK-1 channels and their abundant expression in the CNS, we raise for the first time the possibility of a physiological and/or pathological role for these channels during brain ischemia.

Cell Line↗
PubMed1993

Tetraethylammonium-sensitive apical K+ channels mediating K+ secretion by turtle colon.

1. Apical membrane K+ channels in turtle colon were identified and characterized using current fluctuation analysis. 2. Under short-circuit conditions in NaCl-Ringer solution, the power density spectrum (PDS) of the short-circuit current (Isc) sometimes exhibited a clearly discernible Lorentzian component, indicating spontaneous fluctuations produced by a population of apical ion channels. The Lorentzian component had a characteristic corner frequency (fc) which averaged 10.2 +/- 0.9 Hz (mean +/- S.E.M., n = 20). 3. The power of the spontaneous fluctuations was enhanced (So increased) by manoeuvres that depolarize the apical membrane electrical potential (Va). Discernible fluctuations were enhanced or induced by raising the serosal K+ concentration ([K+]s = 50-115 mM, Na+ replacement), by clamping the transepithelial potential (Vt) to serosa-positive values, or by blocking basolateral K+ channels with Ba2+. 4. Mucosal amiloride (100 microM) attenuated the spontaneous fluctuations observed in NaCl-Ringer solution but had no effect in the presence of serosal high K+, indicating that amiloride did not block the K(+)-permeable channels but these channels resided in the same cells as the amiloride-sensitive Na+ channels. 5. Raising the mucosal K+ concentration attenuated spontaneous fluctuations. 6. In the presence of serosal high K+ and mucosal amiloride, the spontaneous fluctuations were often accompanied by a reversed Isc consistent with K+ secretion. These conditions were used to test the effects of putative channel blockers. 7. Mucosal Ba2+ and tetraethylammonium (TEA+) were effective inhibitors of the spontaneous fluctuations and the reversed Isc. At a concentration of 10 mM, TEA+ was maximally effective but the TEA+ analogues tetramethylammonium (TMA+) and tetrapropylammonium (TPrA+) were much less effective. Mucosal Rb+ or Cs+ did not inhibit at a concentration of 10 mM. 8. Mucosal lidocaine (200 microM), quinidine (200 microM), or diphenylamine-2-carboxylate (DPC, 1 mM) had little or no effect on the spontaneous fluctuations and reversed Isc. Quinine (100 microM), 4-aminopyridine (1 mM), and apamin (100 nM) were also without effect. 9. Mucosal TEA+ (10 mM) abolished the active secretory K+ flux measured in the presence of serosa-positive transepithelial potentials. 10. These experiments identified a population of TEA(+)-sensitive, apical K+ channels which mediate active K+ secretion in turtle colon. Sensitivity to external TEA+ distinguishes these channels from basolateral K+ channels in turtle colon and demonstrates similarity to apical K+ channels in mammalian colon.

Amiloride↗