SEARCH · PubMed Health

Results for “KCNQ1 Potassium Channel”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2005

Dominant-negative I(Ks) suppression by KCNQ1-deltaF339 potassium channels linked to Romano-Ward syndrome.

OBJECTIVE: Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness in addition to cardiac arrhythmias. In this study, we investigate and discuss dominant-negative I(Ks) current reduction by a KCNQ1 deletion mutation identified in a RWS family. METHODS: Single-strand conformation polymorphism analysis and direct sequencing were used to screen LQTS genes for mutations. Mutant KCNQ1 channels were heterologously expressed in Xenopus oocytes, and potassium currents were recorded using the two-microelectrode voltage clamp technique. RESULTS: A heterozygous deletion of three nucleotides (CTT) identified in the KCNQ1 gene caused the loss of a single phenylalanine residue at position 339 (KCNQ1-deltaF339). Electrophysiological measurements in the presence and absence of the regulatory beta-subunit KCNE1 revealed that mutant and wild type forms of an N-terminal truncated KCNQ1 subunit (isoform 2) caused much stronger dominant-negative current reduction than the mutant form of the full-length KCNQ1 subunit (isoform 1). CONCLUSION: This study highlights the functional relevance of the truncated KCNQ1 splice variant (isoform 2) in establishment and mode of inheritance in long QT syndrome. In the RWS family presented here, the autosomal-dominant trait is caused by multiple dominant-negative effects provoked by heteromultimeric channels formed by wild type and mutant KCNQ1-isoforms in combination with KCNE1.

Adult↗

PubMed2001

A kinetic study on the stereospecific inhibition of KCNQ1 and I(Ks) by the chromanol 293B.

1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the gating kinetics of both channels after their heterologous expression in Xenopus oocytes. 2. Kinetic analysis of currents partially blocked with 10 microM of each 293B enantiomer revealed that only 3R,4S-293B but not 3S,4R-293B exhibited a time-dependent block of I(Ks) and KCNQ1 currents, indicating preferential open channel block activity. 3. Inhibition of both KCNQ1 and I(Ks) channels by 3R,4S-293B but not by 3S,4R-293B increased during a 2 Hz train of stimuli. 4. At high extracellular potassium concentrations the inhibition of KCNQ1 by 3R,4S-293B and 3S,4R-293B was unaffected. Drug inhibition of KCNQ1 and I(Ks) by both enantiomers also did not display a significant voltage-dependence, indicating that 293B does not strongly interact with permeant ions in the pore. 5. The inhibitory properties of 3R,4S-293B on I(Ks)-channels but not those of 3S,4R-293B fulfill the theoretical requirements for a novel class III antiarrhythmic drug, i.e. positive use-dependency. This enantiomer therefore represents a valuable pharmacological tool to evaluate the therapeutic efficiency of I(Ks)blockade.

Animals↗

PubMed2003

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype.

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children < or = 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Adolescent↗

PubMed2000

Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors.

1. KCNQ1-4 potassium channels were expressed in mammalian Chinese hamster ovary (CHO) cells stably transfected with M1 muscarinic acetylcholine receptors and currents were recorded using the whole-cell perforated patch technique and cell-attached patch recording. 2. Stimulation of M1 receptors by 10 microM oxotremorine-M (Oxo-M) strongly reduced (to 0-10%) currents produced by KCNQ1-4 subunits expressed individually and also those produced by KCNQ2 + KCNQ3 and KCNQ1 + KCNE1 heteromers, which are thought to generate neuronal M-currents (IK,M) and cardiac slow delayed rectifier currents (IK,s), respectively. 3. The activity of KCNQ2 + KCNQ3, KCNQ2 and KCNQ3 channels recorded with cell-attached pipettes was strongly and reversibly reduced by Oxo-M applied to the extra-patch membrane. 4. It is concluded that M1 receptors couple to all known KCNQ subunits and that inhibition of KCNQ2 + KCNQ3 channels, like that of native M-channels, requires a diffusible second messenger.

Animals↗

PubMed2004

KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.

Potassium channels control the resting membrane potential and excitability of biological tissues. Many voltage-gated potassium channels are controlled through interactions with accessory subunits of the KCNE family through mechanisms still not known. Gating of mammalian channel KCNQ1 is dramatically regulated by KCNE subunits. We have found that multiple segments of the channel pore structure bind to the accessory protein KCNE1. The sites that confer KCNE1 binding are necessary for the functional interaction, and all sites must be present in the channel together for proper regulation by the accessory subunit. Specific gating control is localized to a single site of interaction between the ion channel and accessory subunit. Thus, direct physical interaction with the ion channel pore is the basis of KCNE1 regulation of K+ channels.

Animals↗

PubMed2003

A candidate locus approach identifies a long QT syndrome gene mutation.

Long QT syndrome is an inherited disorder that results in lengthened cardiac repolarization. It can lead to sudden onset of torsades de pointes, ventricular fibrillation, and death. The authors obtained a family history, performed electrocardiograms, and drew blood for DNA extraction and genotyping from 15 family members representing 4 generations of an affected family. Seven individuals demonstrated prolonged QT intervals. The authors used polymorphic short tandem repeat markers at known LQTS loci, which indicated linkage to chromosome 11p15.5 where the potassium channel, KCNQ1, is encoded. Polymerase chain reaction was used to amplify the coding region of KCNQ1. During survey of the KCNQ1 coding region, a G-to-A transition (G502A) was identified. DNA from all clinically affected but from none of the clinically unaffected family members carried the G-to-A transition. The candidate locus approach allowed an efficient mechanism to uncover the potassium channel mutation causing LQTS in this family.

Adolescent↗

PubMed2003

Mutation analysis of potassium channel genes KCNQ1 and KCNH2 in patients with long QT syndrome.

OBJECTIVE: To determine mutations of two common potassium channel subunit genes KCNQ1, KCNH2 causing long QT syndrome (LQTS) in the Chinese. METHODS: Thirty-one Chinese LQTS pedigrees were characterized for mutations in the two LQTS genes, KCNQ1 and KCNH2, by sequencing. RESULTS: Two novel KCNQ1 mutations, S277L in the S5 domain and G306V in the channel pore, and two novel KCNH2 mutations, L413P in the transmembrane domain S1 and L559H in the transmembrane domain S5 were identified. The triggering factors for cardiac events developed in these mutation carriers included physical exercise and excitation. Mutation L413P in KCNH2 was associated with the notched T wave on ECGs. Mutation L559H in KCNH2 was associated with the typical bifid T wave on ECGs. Mutation S277L in KCNQ1 was associated with a high-amplitude T wave and G306V was associated with a low-amplitude T wave. Two likely polymorphisms, IVS11 + 18C > T in KCNQ1 and L520V in KCNH2 were also identified in two LQTS patients. CONCLUSIONS: The mutation rates for both KCNQ1 (6.4%) and KCNH2 (6.4%) are lower in the Chinese population than those from North America or Europe.

Asian People↗

PubMed2002

Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart.

In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.

Action Potentials↗

PubMed2003

Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel.

Beta-adrenergic receptor stimulation increases heart rate and shortens ventricular action-potential duration, the latter effect due in part to a cAMP-dependent increase in the slow outward potassium current (I(Ks)). Mutations in either KCNQ1 or KCNE1, the I(Ks) subunits, are associated with variants (LQT-1 and LQT-5) of the congenital long QT syndrome. We now show that cAMP-mediated functional regulation of KCNQ1/KCNE1 channels, a consequence of cAMP-dependent protein kinase A phosphorylation of the KCNQ1 N terminus, requires coexpression of KCNQ1 with KCNE1, its auxiliary subunit. Further, at least two KCNE1 mutations linked to LQT-5 (D76N and W87R) cause functional disruption of cAMP-mediated KCNQ1/KCNE1-channel regulation despite the response of the substrate protein (KCNQ1) to protein kinase A phosphorylation. Transduction of protein phosphorylation into physiologically necessary channel function represents a previously uncharacterized role for the KCNE1 auxiliary subunit, which can be disrupted in LQT-5.

Amino Acid Sequence↗

PubMed2001

KCNQ potassium channels: physiology, pathophysiology, and pharmacology.

KCNQ genes encode a growing family of six transmembrane domains, single pore-loop, K(+) channel alpha-subunits that have a wide range of physiological correlates. KCNQ1 (KvLTQ1) is co-assembled with the product of the KCNE1 (minimal K(+)-channel protein) gene in the heart to form a cardiac-delayed rectifier-like K(+) current. Mutations in this channel can cause one form of inherited long QT syndrome (LQT1), as well as being associated with a form of deafness. KCNQ1 can also co-assemble with KCNE3, and may be the molecular correlate of the cyclic AMP-regulated K(+) current present in colonic crypt cells. KCNQ2 and KCNQ3 heteromultimers are thought to underlie the M-current; mutations in these genes may cause an inherited form of juvenile epilepsy. The KCNQ4 gene is thought to encode the molecular correlate of the I(K,n) in outer hair cells of the cochlea and I(K,L) in Type I hair cells of the vestibular apparatus, mutations in which lead to a form of inherited deafness. The recently identified KCNQ5 gene is expressed in brain and skeletal muscle, and can co-assemble with KCNQ3, suggesting it may also play a role in the M-current heterogeneity. This review will set this family of K(+) channels amongst the other known families. It will highlight the genes, physiology, pharmacology, and pathophysiology of this recently discovered, but important, family of K(+) channels.

Animals↗

PubMed2003

Structural determinants and biophysical properties of HERG and KCNQ1 channel gating.

The delayed rectifier K(+) currents, I(Kr) and I(Ks,) play a critical role in modulating the plateau phase of the cardiac action potential. HERG encodes the alpha-subunit of channels underlying I(Kr), while I(Ks) is composed of subunits encoded by KCNQ1 and KCNE1. Mutations in any of these genes cause the long QT syndrome, a disorder of myocellular repolarization that predisposes affected individuals to life-threatening arrhythmias. Elucidation of the molecular basis of these currents has led to significant advancements in our understanding of fundamental properties of channel function. This review summarizes the current state of knowledge regarding the structural determinants and biophysical properties of HERG and KCNQ1 channels.

Animals↗

PubMed2005

hKCNE4 inhibits the hKCNQ1 potassium current without affecting the activation kinetics.

All five members of the KCNE beta-subunit family are capable of modulating the KCNQ1 potassium current. We have previously published that the murine variant of KCNE4 inhibits the human KCNQ1 current [J. Physiol. 542 (2002) 119]. Recently, this finding has been challenged by Teng et al., stating that the human variant of KCNE4 does not attenuate the KCNQ1 current but does slightly modulate the activation kinetics of the channel after expression in Xenopus laevis oocytes [Biochem. Biophys. Res. Commun. 303 (2003) 808]. In the present study, a detailed investigation on the ability of human and murine KCNE4 to affect either human or murine KCNQ1 currents has been performed. We find that the hKCNE4 subunit drastically inhibits the hKCNQ1 current after expression in X. laevis oocytes. This inhibitory effect is also observed for both hKCNE4 and mKCNE4 when either of these subunits is co-expressed with mKCNQ1. Analyses of the current properties of hKCNQ1 revealed that activation kinetics are independent of the presence of hKCNE4. hKCNE4 has, however, the ability to prevent the inactivation observed for the KCNQ1 current. Based upon previous studies and the present results, it is concluded that both hKCNE4 and mKCNE4 have a drastic inhibitory impact on both hKCNQ1 and mKCNQ1 currents.

Animals↗

PubMed2005

Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels.

KCNQ1 (Kv 7.1) alpha-subunits and KCNE1 beta-subunits co-assemble to form channels that conduct the slow delayed rectifier K+ current (IKs) in the heart. Mutations in either subunit cause long QT syndrome (LQTS), an inherited disorder of cardiac repolarization. Here, the functional consequences of the LQTS-associated missense mutation V310I and several nearby residues were determined. Val310 is located at the base of the pore helix of KCNQ1, two residues below the TIGYG signature sequence that defines the K+ selectivity filter. Channels were heterologously expressed in Xenopus laevis oocytes and currents were recorded using the two-microelectrode voltage-clamp technique. V310I KCNQ1 reduced IKs amplitude when co-expressed with wild-type KCNQ1 and KCNE1 subunits. Val310 was also mutated to Gly, Ala or Leu to explore the importance of amino acid side chain volume at this position. Like V310I, V310L KCNQ1 channels gated normally. Unexpectedly, V310G and V310A KCNQ1 channels inactivated strongly and did not close normally in response to membrane hyperpolarization. Based on a homology model of the KCNQ1 channel pore, we speculate that the side group of residue 310 can interact with specific residues in the S5 and S6 domains to alter channel gating. When volume of the side chain is small, the stability of the closed state is disrupted and the extent of channel inactivation is enhanced. We mutated putative interacting residues in S5 and S6 and found that mutant Leu273 and Phe340 channels also can disrupt close states and modify inactivation. Together these findings indicate the importance of a putative pore helix-S5-S6 interaction for normal KCNQ1 channel deactivation and confirm its role in KCNQ1 inactivation. Disturbance of these interactions might underly LQTS associated with KCNQ1 mutant channels.

Amino Acid Sequence↗

PubMed2005

De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero.

OBJECTIVE: We describe a genetic basis for atrial fibrillation and short QT syndrome in utero. Heterologous expression of the mutant channel was used to define the physiological consequences of the mutation. METHODS: A baby girl was born at 38 weeks after induction of delivery that was prompted by bradycardia and irregular rythm. ECG revealed atrial fibrillation with slow ventricular response and short QT interval. Genetic analysis identified a de novo missense mutation in the potassium channel KCNQ1 (V141M). To characterize the physiological consequences of the V141M mutation, Xenopus laevis oocytes were injected with cRNA encoding wild-type (wt) KCNQ1 or mutant V141M KCNQ1 subunits, with or without KCNE1. RESULTS: Ionic currents were recorded using standard two-microelectrode voltage clamp techniques. In the absence of KCNE1, wtKCNQ1 and V141M KCNQ1 currents had similar biophysical properties. Coexpression of wtKCNQ1+KCNE1 subunits induced the typical slowly activating and voltage-dependent delayed rectifier K(+) current, I(Ks). In contrast, oocytes injected with cRNA encoding V141M KCNQ1+KCNE1 subunits exhibited an instantaneous and voltage-independent K(+)-selective current. Coexpression of V141M and wtKCNQ1 with KCNE1 induced a current with intermediate biophysical properties. Computer modeling showed that the mutation would shorten action potential duration of human ventricular myocytes and abolish pacemaker activity of the sinoatrial node. CONCLUSIONS: The description of a novel, de novo gain of function mutation in KCNQ1, responsible for atrial fibrillation and short QT syndrome in utero indicates that some of these cases may have a genetic basis and confirms a previous hypothesis that gain of function mutations in KCNQ1 channels can shorten the duration of ventricular and atrial action potentials.

Action Potentials↗

PubMed2003

A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly.

Mutations in KCNQ K(+) channel genes underlie several human pathologies. KCNQ alpha-subunits form either homotetramers or hetero-oligomers with a restricted subset of other KCNQ alpha-subunits or with KCNE beta-subunits. KCNQ1 assembles with KCNE beta-subunits but not with other KCNQ alpha-subunits. By contrast, KCNQ3 interacts with KCNQ2, KCNQ4 and KCNQ5. Using a chimaeric strategy, we show that a cytoplasmic carboxy-terminal subunit interaction domain (sid) suffices to transfer assembly properties between KCNQ3 and KCNQ1. A chimaera (KCNQ1-sid(Q3)) carrying the si domain of KCNQ3 within the KCNQ1 backbone interacted with KCNQ2, KCNQ3 and KCNQ4 but not with KCNQ1. This interaction was shown by enhancement of KCNQ2 currents, testing for dominant-negative effects of pore mutants, determining its effects on surface expression and co-immunoprecipitation experiments. Conversely, a KCNQ3-sid(Q1) chimaera no longer affects KCNQ2 but interacts with KCNQ1. We conclude that the si domain suffices to determine the subunit specificity of KCNQ channel assembly.

Amino Acid Sequence↗

PubMed2001

The small conductance K+ channel, KCNQ1: expression, function, and subunit composition in murine trachea.

The gene KCNQ1 encodes a K(+) channel alpha-subunit important for cardiac repolarization, formerly known as K(v)LQT1. In large and small intestine a channel complex consisting of KCNQ1 and the beta-subunit KCNE3 (MiRP2) is known to mediate the cAMP-activated basolateral K(+) current, which is essential for luminal Cl(-) secretion. Northern blot experiments revealed an expression of both subunits in lung tissue. However, previous reports suggested a role of KCNE1 (minK, Isk) but not KCNE3 in airway epithelial cells. Here we give evidence that KCNE1 is not detected in murine tracheal epithelial cells and that Cl(-) secretion by these cells is not reduced by the knock-out of the KCNE1 gene. In contrast we show that a complex consisting of KCNQ1 and KCNE3 probably forms a basolateral K(+) channel in murine tracheal epithelial cells. As described for colonic epithelium, the current through KCNQ1 complexes in murine trachea is specifically inhibited by the chromanol 293B. A 293B-sensitive current was present after stimulation with forskolin and agonists that increase Ca(2+) as well as after administration of the pharmacological K(+) channel activator, 1-EBIO. A 293B-inhibitable current was already present under control conditions and reduced after administration of amiloride indicating a role of this K(+) channel not only for Cl(-) secretion but also for Na(+) reabsorption. We conclude that at least in mice a KCNQ1 channel complex seems to be the dominant basolateral K(+) conductance in tracheal epithelial cells.

Adenosine Triphosphate↗

PubMed2004

A structural requirement for processing the cardiac K+ channel KCNQ1.

Normal membrane protein function requires trafficking from the endoplasmic reticulum. Here, we studied processing of the KCNQ1 channel mutated in LQT1, the commonest form of the long QT syndrome. Serial C terminus truncations identified a small region (amino acids (aa) 610-620) required for normal cell surface expression. Non-trafficked truncations assembled as tetramers but were nevertheless retained in the endoplasmic reticulum. Further mutagenesis did not identify specific residues mediating channel processing; cell surface expression was preserved with the mutation of known trafficking motifs in the channel and with alanine scanning across aa 610-620. Structural prediction algorithms place aa 610-620 at the C-terminal end of an alpha-helix (aa 586-618) that includes a leucine zipper and is part of a coiled coil. Mutants disrupting the leucine zipper but preserving the predicted coiled coil reached the cell surface, whereas those disrupting the coil did not. These data suggest that specific protein-protein interactions are required for normal channel processing. Further biochemical studies ruled out three candidate proteins, namely KCNE1, yotiao, and KCNQ1 itself, as effectors of this coiled coil-mediated trafficking. Four LQT1 mutations within this helix generated little or no current and were not expressed on the cell surface, whereas LQT1 mutations in adjacent residues, which produce a milder clinical phenotype, generate only slightly reduced current and are expressed on the cell surface. These data suggest that mutations within this domain cause human disease by interfering with normal channel processing. More generally, we have identified a domain whose structural integrity is required for normal surface expression of the KCNQ1 channel.

Alanine↗

PubMed2004

Effects of KCNQ1 channel blocker, 293B, on the acetylcholine-induced Cl- secretion of rat pancreatic acini.

In rat pancreatic acini (RPAs), acetylcholine (ACh) typically induces a tonic depolarization of membrane potential (Vm) via increasing cytoplasmic Ca2+ concentration and subsequent activation of Cl- channels. In this study, to investigate the role of K+ channels during the ACh-induced Cl- secretion, the intracellular Cl- concentration ([Cl-]i) of RPAs was monitored using SPQ, a fluorescent dye quenchable by Cl-, and the effects of K+ channel blockers were examined. Also, the secretion of fluid and enzyme from the whole pancreas of rat was measured. The fluorescence of RPAs loaded with SPQ (FSPQ) was slightly increased by the application of ACh (ACh-Delta FSPQ), indicating net secretion of Cl-. However, the relative change of FSPQ normalized to the control fluorescence (F/F0) of RPAs was only about 20% of the effect observed in rat submandibular gland acinus. The ACh-Delta FSPQ of RPAs was not influenced by the pretreatment with 293B (20 micromol/L), a blocker of KCNQ-type K+ channels. Even the cocktail of K+ channel blockers (10 mmol/L TEA, 3 mmol/L Ba2+, 20 micromol/L 293B) exerted only minute inhibitory effects on ACh-Delta FSPQ in RPAs. In the vascularly perfused rat pancreas, the fluid and enzyme secretion induced by ACh was directly measured. 293B and HMR-1556, both specific blockers of KCNQ1 channel, did not block but even enhanced the secretion of fluid and amylase. These results suggest that the role of KCNQ1 channels may not be essential in the Ca2+-mediated Cl- secretion in rat pancreatic acini.

Acetylcholine↗