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Results for “Potassium Channel Blockers”

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PubMed1997

Effect of activators and inhibitors of K+ channels on insulin secretion in the amphibian pancreas.

The aim of this study was to obtain pharmacological evidence for the presence and participation of K+ channels in amphibian pancreatic islets. Pancreases from the toad Bufo arenarum were thus incubated with activators or blockers of K+ channels and the immunoreactive insulin released into the medium was measured by radioimmunoassay. Two K(+)-ATP channel openers (diazoxide and BPDZ44) inhibited; while a K(+)-ATP channel blocker (tolbutamide) and metabolizable sugars (glucose, glyceraldehyde) significantly stimulated the output of insulin. Although a nonmetabolizable sugar (galactose) failed to increase insulin release, dinitrophenol decreased the secretagogue effect of glucose. By contrast, although somatostatin and clonidine blocked the release of insulin, tetraethylammonium significantly stimulated secretion. For each compound tested, the effects on both insulin secretion and B-cell K+ channel activity were similar to those observed in the mammalian pancreas. These findings point to the existence of mammalian-like K+ channels in the B-cells of some amphibians.

Animals↗

PubMed2004

Anuroctoxin, a new scorpion toxin of the alpha-KTx 6 subfamily, is highly selective for Kv1.3 over IKCa1 ion channels of human T lymphocytes.

The physiological function of T lymphocytes can be modulated selectively by peptide toxins acting on Kv1.3 K(+) channels. Because Kv1.3-specific peptide toxins are considered to have a significant therapeutic potential in the treatment of autoimmune diseases, the discovery of new toxins is highly motivated. Through chromatographic procedures and electrophysiological assays, using patch-clamp methodology, the isolation of a novel peptide named anuroctoxin was accomplished using the venom of the Mexican scorpion Anuroctonus phaiodactylus. It has 35 amino acid residues with a molecular weight of 4082.8, tightly bound by four disulfide bridges whose complete covalent structure was determined. It has a pyroglutamic acid at the N-terminal region and an amidated C-terminal residue. Sequence comparison and phylogenetic clustering analysis classifies anuroctoxin into subfamily 6 of the alpha-KTx scorpion toxins (systematic name, alpha-KTx 6.12). Patch-clamp experiments show that anuroctoxin is a high-affinity blocker of Kv1.3 channels of human T lymphocytes with a K(d) of 0.73 nM, and it does not block the Ca(2+)-activated IKCa1 K(+) channels. These two channels play different but important roles in T-lymphocyte activation. Furthermore, the toxin practically does not inhibit Shaker IR, mKv1.1, and rKv2.1 channels, whereas the affinity of anuroctoxin for hKv1.2 is almost an order of magnitude smaller than for Kv1.3. The pharmacological profile and the selectivity of this new toxin for Kv1.3 over IKCa1 may provide an important tool for the modulation of the immune system, especially in cases in which selective inhibition of Kv1.3 is required.

Animals↗

PubMed2002

Ototoxic side-effects of the I(Ks)-channel blocker HMR1556.

The inhibitor of I(Ks)-channels, HMR1556, a potentially antiarrhythmic drug, might possess ototoxic side-effects. The I(Ks)-channels are not only expressed in the heart but also in the stria vascularis of the inner ear and in the dark cells of the vestibular organ. Therefore possible effects of HMR1556 on hearing were studied in cats. Thresholds and intensity function of the cochlear action potential (CAP) were used as criteria. In addition to effects of the drug on heart rate and ECG, a substantial elevation of hearing thresholds and a shift in CAP intensity functions were observed. There was a clear dose-effect relationship. The hearing impairment observed showed a tendency for recovery. It is concluded that inhibitors of I(Ks)-channels may generally exert ototoxic effects provided they can reach the cochlear spaces.

Action Potentials↗

PubMed1998

Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost.

The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel blocker, glibenclamide significantly augmented the response to iloprost but not cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by indomethacin, suggesting that iloprost relaxation is counterbalanced by activation of EP1 receptors, in part through a constrictor prostaglandin. We conclude that BKCa channels play an important role in mediating the effects of iloprost and cicaprost and raises the possibility that cyclic AMP-independent pathways might be involved.

Animals↗

PubMed2005

Nicorandil inhibits serum starvation-induced apoptosis in vascular endothelial cells.

The Impact Of Nicorandil in Angina (IONA) randomized trial showed a significant reduction in coronary events, in patients with stable angina treated with a KATP channel opener, nicorandil. However, the impact of nicorandil on endothelial apoptosis remains to be examined. We tested the hypothesis that nicorandil has anti-apoptotic effects in endothelial cells (ECs). Apoptosis was induced by serum starvation in the culture media in human umbilical vein endothelial cells. We examined the effects of nicorandil on endothelial cell apoptosis. Cell viability after serum starvation was significantly higher in the nicorandil-treated group compared with the control group (81 +/- 8% vs. 63 +/- 3%, P < 0.01). Apoptosis, as detected by caspase 3 activation and Hoechst 33258 assay, induced by serum starvation was also effectively abrogated by the treatment of nicorandil (100 muM). The protective effects of nicorandil on endothelial survival were significantly inhibited by a specific mitochondrial KATP channel blocker, 5-Hydroxydecanoic acid. A mitochondrial permeability transition pore activator significantly abolished the anti-apoptotic effect of nicorandil in endothelial cells, indicating that the mechanism of protective effect of nicorandil is involved in the mitochondrial apoptotic pathway although it affects neither Bcl-2 nor Bax protein expression levels. In conclusion, nicorandil inhibits serum starvation-induced endothelial cell apoptosis possibly through mitochondrial KATP channels.

Angina Pectoris↗

PubMed2002

Expression of voltage-gated K+ channels in human atrium.

Voltage-gated K(+) channels underlie repolarisation of the cardiac action potential and represent a potential therapeutic target in the treatment of cardiac dysrhythmias. However, very little is known about the relative expression of K(+) channel subunits in the human myocardium. We used a semi-quantitative RT-PCR technique to examine the relative expression of mRNAs for the voltage-gated K(+) channel subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, Kv4.3, KvLQT1, HERG and IsK in samples of human atrial appendage. Data were expressed as a percentage expression density relative to an 18S ribosomal RNA internal standard. The most abundant K(+) channel mRNAs were Kv4.3 (80.7 +/- 10.1 %), Kv1.5 (69.7 +/- 11.2 %) and HERG (55.9 +/- 21.5 %). Significant expression of KvLQT1 (33.5 +/- 5.5 %,) and Kv1.4 (26.7 +/- 9.6 %) was also detected. Levels of mRNAs for Kv1.2 and IsK were very low and neither Kv2.1 nor Kv4.2 mRNA were detected in any experiments. Whole-cell patch-clamp techniques were used to examine the outward currents of isolated human atrial myocytes at 37 degrees C. These recordings demonstrated the existence of transient (I(to1)) and sustained (I(so)) outward currents in isolated human atrial myocytes. I(to1), and not I(so), showed voltage-dependent inactivation during 100 ms pre-pulses. Both I(to1) and I(so) were inhibited by high concentrations (2 mM) of the K(+) channel blocker, 4-aminopyridine (4-AP). However, lower concentrations of 4-AP (10 microM) inhibited I(so) selectively. I(to1) recovered from inactivation relatively rapidly (tao approximately 21 ms). These data, with published information regarding the properties of expressed K(+) channels, suggest that Kv4.3 represents the predominant K(+) channel subunit underlying I(to1) with little contribution of Kv1.4. The sensitivity of Iso to very low concentrations of 4-aminopyridine and the relatively low expression of mRNA for Kv1.2 and Kv2.1 is consistent with the major contribution of Kv1.5 to this current. The physiological significance of the expression of KvLQT1 and Kv1.4 mRNA in the human atrium warrants further investigation.

4-Aminopyridine↗

PubMed1996

Endothelin-1 can reduce infarct size through protein kinase C and KATP channels in the isolated rat heart.

OBJECTIVE: Protection from ischaemic preconditioning (IP) is dependent on activation of protein kinase C (PKC), and preconditionings protection can be mimicked by stimulation of various membrane receptors which are known to activate PKC. It is well known that KATP channel activation is cardioprotective. We tested the hypothesis that preischaemic treatment with endothelin-1 (ET-1) can protect against infarction by a PKC-dependent mechanism and by activating KATP channels. METHODS: Buffer-perfused isolated rat hearts were subjected to 30 min regional ischaemia and 120 min reperfusion. Risk zone was determined by fluorescent particles, and infarct size by TTC staining. RESULTS: Treatment with ET-1 in a dose of 1 nM prior to ischaemia significantly reduced infarct size in % of the risk zone compared to the control group (infarct size: 14.1 +/- 2.6 vs. 41.9 +/- 3.4%), while ET-1 0.1 nM did not protect (infarct size: 40.9 +/- 3%). AS the protective dose of ET-1 resulted in a significant reduction of coronary flow, a control group with a similar preischaemic flow-reduction was included (infarct size: 48.1 +/- 4.2%). Both the nonselective ETA/ETB receptor antagonist bosentan (1 microM) and the ET(A)-receptor-selective antagonist BQ 123 (2 microM) abolished protection from ET-1 (infarct size: 43.3 +/- 3.5 and 41.3 +/- 3.3%, respectively), as did the PKC inhibitor chelerythrine (2 microM) (infarct size: 41.1 +/- 5.2%) and the KATP blocker 5-hydroxydecanoate (infarct size: 41.7 +/- 2.9%). None of the ET receptor antagonists bosentan and BQ-123 influenced infarct size alone (infarct size: 42.7 +/- 2.5 and 41.3 +/- 3.3%, respectively). IP, similarly to ET-1, reduced infarct size (infarct size: 6.1 +/- 1.4%), but the nonselective ET receptor antagonist bosentan did not interfere with preconditioning's protection (infarct size: 13.2 +/- 4.3%). CONCLUSIONS: ET-1 treatment prior to ischaemia can protect against infarction via ETA receptors by a PKC-dependent mechanism and by activating KATP channels, but ET does not mediate IP in the isolated rat heart.

Alkaloids↗

PubMed1999

A marine snail neurotoxin shares with scorpion toxins a convergent mechanism of blockade on the pore of voltage-gated K channels.

kappa-Conotoxin-PVIIA (kappa-PVIIA) belongs to a family of peptides derived from a hunting marine snail that targets to a wide variety of ion channels and receptors. kappa-PVIIA is a small, structurally constrained, 27-residue peptide that inhibits voltage-gated K channels. Three disulfide bonds shape a characteristic four-loop folding. The spatial localization of positively charged residues in kappa-PVIIA exhibits strong structural mimicry to that of charybdotoxin, a scorpion toxin that occludes the pore of K channels. We studied the mechanism by which this peptide inhibits Shaker K channels expressed in Xenopus oocytes with the N-type inactivation removed. Chronically applied to whole oocytes or outside-out patches, kappa-PVIIA inhibition appears as a voltage-dependent relaxation in response to the depolarizing pulse used to activate the channels. At any applied voltage, the relaxation rate depended linearly on the toxin concentration, indicating a bimolecular stoichiometry. Time constants and voltage dependence of the current relaxation produced by chronic applications agreed with that of rapid applications to open channels. Effective valence of the voltage dependence, zdelta, is approximately 0.55 and resides primarily in the rate of dissociation from the channel, while the association rate is voltage independent with a magnitude of 10(7)-10(8) M-1 s-1, consistent with diffusion-limited binding. Compatible with a purely competitive interaction for a site in the external vestibule, tetraethylammonium, a well-known K-pore blocker, reduced kappa-PVIIA's association rate only. Removal of internal K+ reduced, but did not eliminate, the effective valence of the toxin dissociation rate to a value <0.3. This trans-pore effect suggests that: (a) as in the alpha-KTx, a positively charged side chain, possibly a Lys, interacts electrostatically with ions residing inside the Shaker pore, and (b) a part of the toxin occupies an externally accessible K+ binding site, decreasing the degree of pore occupancy by permeant ions. We conclude that, although evolutionarily distant to scorpion toxins, kappa-PVIIA shares with them a remarkably similar mechanism of inhibition of K channels.

Animals↗

PubMed2006

M-like K+ currents in type I hair cells and calyx afferent endings of the developing rat utricle.

Type I vestibular hair cells have large K+ currents that, like neuronal M currents, activate negative to resting potential and are modulatable. In rodents, these currents are acquired postnatally. In perforated-patch recordings from rat utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had a steady-state K+ conductance (g(-30)) with a half-activation voltage (V1/2) of -30 mV. The size and activation range did not change in maturing type II cells, but, by P16, type I cells had added a K conductance that was on average fourfold larger and activated much more negatively. This conductance may comprise two components: g(-60) (V1/2 of -60 mV) and g(-80) (V1/2 of -80 mV). g(-80) washed out during ruptured patch recordings and was blocked by a protein kinase inhibitor. M currents can include contributions from KCNQ and ether-a-go-go-related (erg) channels. KCNQ and erg channel blockers both affected the K+ currents of type I cells, with KCNQ blockers being more potent at younger than P7 and erg blockers more potent at older than P16. Single-cell reverse transcription-PCR and immunocytochemistry showed expression of KCNQ and erg subunits. We propose that KCNQ channels contribute to g(-30) and g(-60) and erg subunits contribute to g(-80). Type I hair cells are contacted by calyceal afferent endings. Recordings from dissociated calyces and afferent endings revealed large K+ conductances, including a KCNQ conductance. Calyx endings were strongly labeled by KCNQ4 and erg1 antisera. Thus, both hair cells and calyx endings have large M-like K+ conductances with the potential to control the gain of transmission.

Animals↗

PubMed1997

Hyperpolarization of hepatocytes by 2,5-AM: implications for hepatic control of food intake.

Because 2,5-anhydro-D-mannitol (2,5-AM) seems to stimulate feeding by acting on the liver and because the hepatic membrane potential has been suggested to play an important role in control of feeding ("potentiostatic" hypothesis), we investigated the effect of 2,5-AM on the membrane potential of liver cells with microelectrodes using a superfused liver slice technique. 2,5-AM (2.5 mM), which reduces intracellular ATP in rat liver, hyperpolarized the liver cell membrane in mouse and rat liver slices by 4-7 mV. This hyperpolarization was reversed by quinine (1 mM), an unspecific blocker of Ca2+-dependent K+ channels, and abolished by apamin (20 nM), a blocker of Ca2+-activated K+ channels with low conductance. Amiloride at 10(-3) M, but not at 10(-6) M, or a low-Na medium (26 mM) also eliminated the hyperpolarization. The K+ channel blockers cetiedil (50 microM), glibenclamide (30 microM), and Ba2+ (5 mM); flufenamic acid (100 microM), a blocker of nonselective cation channels; and ouabain (1 mM), an inhibitor of the Na+-K+-adenosinetriphosphatase, did not significantly influence the 2,5-AM-induced hyperpolarization. It is concluded that 2,5-AM hyperpolarizes the liver cell membrane by activating Ca2+-dependent K+ channels. This activation seems to be impaired when the Na+/H+ exchanger is inhibited by amiloride or a low-Na+ medium. The findings also imply that the hyperphagic effect of 2,5-AM observed in rats is not associated with a decrease in the hepatic membrane potential, as postulated by the potentiostatic hypothesis.

Amiloride↗

PubMed2003

Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1-based K(ATP) channels.

BACKGROUND AND PURPOSE: ATP-sensitive K+ (K(ATP)) channels have been implicated in the mechanism of neuronal ischemic preconditioning. To evaluate the role of neuronal/beta-cell-type K(ATP) channels, SUR1 null (Sur1KO) mice lacking (K(IR)6.x/SUR1)(4) K(ATP) channels were subjected to a preconditioning protocol with the use of double carotid occlusion. METHODS: Wild-type C57BL/6 and Sur1KO mice were subjected to a double carotid block for 40 minutes with or without a 20-minute preconditioning block. After a 10-day reperfusion period, damage was assessed histologically in the hippocampal CA1, CA2, and CA3 areas and in the dentate gyrus. The neuroprotective effects of intracerebroventricular injections of diazoxide, which selectively affects mitochondria versus opening SUR1-type K(ATP) channels, and 5-hydroxydecanoate, a selective blocker of mitoK(ATP) channels, were evaluated with the same protocol. RESULTS: Neurons in the CA1 region of both Sur1KO and wild-type animals subjected to a 20-minute ischemic insult were protected equally from neuronal damage produced by a subsequent 40-minute ischemic period. Pretreatment with diazoxide protected both Sur1KO and wild-type neurons, while 5-hydroxydecanoate augmented neurodegeneration in both strains of animals when administered before a 20-minute bout of ischemia. CONCLUSIONS: SUR1-based K(ATP) channels are not obligatory for neuronal preconditioning or augmentation of neurodegeneration by 5-hydroxydecanoate.

Adenosine Triphosphate↗

PubMed2002

Pharmacological evidence for the activation of K(+) channels by diclofenac.

The involvement of K(+) channels in the antinociceptive action of diclofenac was assessed in the formalin test. Local administration of diclofenac produced a dose-dependent antinociceptive effect due to a local action because drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with glibenclamide and tolbutamide (ATP-sensitive K(+) channel inhibitors), charybdotoxin and apamin (large- and small-conductance Ca(2+)-activated K(+) channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K(+) channel inhibitors) prevented diclofenac-induced antinociception. Given alone, K(+) channel inhibitors did not modify formalin-induced nociceptive behavior. Pinacidil (an ATP-sensitive K(+) channel opener) also produced antinociception which was blocked by glibenclamide. The peripheral antinociceptive effect of morphine (positive control) was blocked by glibenclamide and 4-aminopyridine but not by charybdotoxin or apamin. The results suggest that the peripheral antinociceptive effect of diclofenac may result from the activation of several types of K(+) channels, which may cause hyperpolarization of peripheral terminals of primary afferents.

4-Aminopyridine↗

PubMed2006

Functional expression of Kir4.1 channels in spinal cord astrocytes.

Spinal cord astrocytes (SCA) have a high permeability to K+ and hence have hyperpolarized resting membrane potentials. The underlying K+ channels are believed to participate in the uptake of neuronally released K+. These K+ channels have been studied extensively with regard to their biophysics and pharmacology, but their molecular identity in spinal cord is currently unknown. Using a combination of approaches, we demonstrate that channels composed of the Kir4.1 subunit are responsible for mediating the resting K+ conductance in SCA. Biophysical analysis demonstrates astrocytic Kir currents as weakly rectifying, potentiated by increasing [K+]o, and inhibited by micromolar concentrations of Ba2+. These currents were insensitive to tolbutemide, a selective blocker of Kir6.x channels, and to tertiapin, a blocker for Kir1.1 and Kir3.1/3.4 channels. PCR and Western blot analysis show prominent expression of Kir4.1 in SCA, and immunocytochemistry shows localization Kir4.1 channels to the plasma membrane. Kir4.1 protein levels show a developmental upregulation in vivo that parallels an increase in currents recorded over the same time period. Kir4.1 is highly expressed throughout most areas of the gray matter in spinal cord in vivo and recordings from spinal cord slices show prominent Kir currents. Electrophysiological recordings comparing SCA of wild-type mice with those of homozygote Kir4.1 knockout mice confirm a complete and selective absence of Kir channels in the knockout mice, suggesting that Kir4.1 is the principle channel mediating the resting K+ conductance in SCA in vitro and in situ.

Animals↗

PubMed2005

Pharmacological evidence for the activation of Ca2+-activated K+ channels by meloxicam in the formalin test.

The possible participation of K+ channels in the antinociceptive action of meloxicam was assessed in the 1% formalin test. Local peripheral administration of meloxicam produced a dose-dependent antinociception only during the second phase of the formalin test. K+ channel blockers alone did not modify formalin-induced nociceptive behavior. However, local peripheral pretreatment of the paw with charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel inhibitors, respectively), 4-aminopyridine and tetraethylammonium (non-selective voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented meloxicam-induced antinociception. It is concluded that meloxicam could open large- and small-conductance Ca2+-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since non-selective inhibitors were used the data await further confirmation.

4-Aminopyridine↗

PubMed1999

K(+) secretion in rat distal jejunum.

The Ussing chamber technique was used to measure unidirectional Rb(+) fluxes under short-circuit conditions across tissue sheets from proximal, central, and distal jejunum of rats. Whereas the proximal and central parts of the jejunum did not show any net transport of Rb(+), there was a net secretion of around 0.2 micromol hr(-1) cm(-2) in the distal segment. This secretion could not be influenced significantly by mucosal application of K(+) channel blockers such as Ba(2+) (5 mm), tetraethylammonium (20 mm) or quinine (1 mm). Serosal ouabain (1 mm) blocked net secretion by increasing mucoserosal flux. Blockers of H(+)/K(+) ATPases could not alter net fluxes of Rb(+). Stimulation of Cl(-) secretion by forskolin (10 microm) or of Na(+) absorption by serine (10 mm) failed to influence the observed secretion of Rb(+). Adrenaline (10 microm) also had no effect on Rb(+) fluxes. Blocking Na(+)/H(+) exchange by 5-(N-Ethyl-N-isopropyl)-amilorid (100 microm) blocked net secretion by increasing mucoserosal flux, as did the addition of Na(+) acetate (30 mm) to the mucosal solution. We conclude that the distal jejunum of the rat secretes K(+) under short-circuit conditions. This secretion does not seem to occur via K(+) channels, but through a pH dependent mechanism.

Animals↗

PubMed2003

Large conductance Ca2+-activated K+ channels sense acute changes in oxygen tension in alveolar epithelial cells.

The rise in alveolar oxygen tension (PO(2)) that occurs as the newborn infant takes its first breaths induces removal of liquid from the lung lumen due to ion transport across the alveolar epithelium and the activity of alveolar Na(+) channel (ENaC). In the present study, we have aimed to identify an ion conductance in alveolar epithelial A549 cells that responds to acute changes in PO(2). Variation in PO(2) did not affect single-channel ENaC activity. However, in these cells we have detected single-channel conductance having properties similar to those of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Reverse transcriptase-polymerase chain reaction and Western blotting demonstrated presence of alpha-BKCa channel subunit and iberiotoxin, a blocker of BK(Ca) channels, inhibited whole cell K(+) current. Chronic changes in PO(2) did not affect expression, recruitment, or function of BK(Ca) channels in A549 cells. In contrast, acute changes of PO(2) regulated the BK(Ca) channel activity by controlling the channel mean open time. This effect of PO(2) was insensitive to inhibitor of flavoproteins, diphenylene iodinium. In addition, decrease in PO(2) and iberiotoxin induced membrane depolarization and Ca(2+) oscillations in A549 cells. We conclude that BK(Ca) channels serve as oxygen sensors in human alveolar A549 epithelial cells.

Calcium↗

PubMed1998

The role of BK(Ca) channels in the nitric oxide-mediated regulation of adrenal catecholamine secretion.

We examined whether high conductance Ca2+-activated K+ (BK(Ca)) channels are involved in the modulatory action of nitric oxide (NO) on the secretion of adrenal catecholamines in response to splanchnic nerve stimulation and acetylcholine in anesthetized dogs. The NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e (NOC 7), the BK(Ca) channel blocker charybdotoxin and acetylcholine were administered intraarterially (i.a.) into the adrenal gland. NOC 7 infusion (2 microg min(-1)) inhibited increases in catecholamine output induced by splanchnic nerve stimulation (1-3 Hz) and acetylcholine (0.75-3 microg). Charybdotoxin infusion (100 ng min(-1)) did not affect increases in catecholamine output induced by splanchnic nerve stimulation and acetylcholine. Charybdotoxin blocked the NOC 7-induced inhibition of increases in catecholamine output induced by splanchnic nerve stimulation but not by acetylcholine. These results suggest that NO may inhibit the secretion of adrenal catecholamines induced by splanchnic nerve stimulation through activation of BK(Ca) channels.

Acetylcholine↗

PubMed1998

Functional expression of a Ca2+-activated K+ channel in Xenopus oocytes injected with RNAs from the rat testis.

The present study investigated the feasibility of using Xenopus oocytes to express sperm ion channel by injection of RNAs extracted from the rat testis. The RNA-injected oocytes expressed an outwardly rectifying current which was dependent on K+ concentration and inhibitable by K+ channel blockers, charybdotoxin (CTX) and tetraethylammonium (TEA). The Ca2+ ionophore, ionomycin, could also stimulate current activation with similar current characteristics in the RNA-injected oocytes, suggesting the expression of a Ca2+-activated K+ channel. Immunolocalization indicated predominant Ca2+-activated K+ channel immunoreactivity associated with spermatogenic cells. Reverse transcriptase-polymerase chain reaction studies confirmed the expression of the Ca2+-activated K+ channel mRNA in isolated spermatogenic cells. Our results suggest that ion channels and/or receptors of spermatogenic cells could be investigated using the Xenopus oocyte as an expression system. The present study also suggests that sperm may possess a Ca2+-activated K+ channel which has been implicated in the process of sperm activation and gamete interaction.

Animals↗