Biomedical subjects

S Ohya

Publications and source records attributed to S Ohya.

At least 19 recordsLinked to original sources

PubMed2007

C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.

Animals↗

PubMed2006

Pharmacological and molecular evidence for the involvement of Kv4.3 in ultra-fast activating K+ currents in murine portal vein myocytes.

BACKGROUND AND PURPOSE: The aim of this study was to determine the molecular identity of a transient K+ current (termed IUF) in mouse portal vein myocytes using pharmacological and molecular tools. EXPERIMENTAL APPROACH: Whole cell currents were recorded using the ruptured patch con from either acutely dispersed single smooth muscle cells from the murine portal vein or human embryonic kidney cells. Reverse transcriptase polymerase reaction (RT-PCR) experiments were undertaken on RNA isolated from mouse portal vein using primers specific for various voltage-dependent K+ channels, auxillary subunits and calcium-binding proteins. Immunocytochemistry was undertaken using an antibody specific for Kv4.3. KEY RESULTS: IUF had a mean amplitude at +40 mV of 558 +/- 50 pA (n = 32) with a mean time to peak at +40 mV of approximately 4 ms. IUF activated and inactivated with a half maximal voltage of -12 +/- 2 mV and -85 +/- 2 mV, respectively. IUF was relatively resistant to 4-aminopyridine (5 mM produced 30 +/- 6 % block at +20 mV) but was inhibited effectively by flecainide (IC50 value was 100 nM) and phrixotoxin II. This pharmacological profile is consistent with IUF being comprised of Kv4.x proteins and this is supported by the results from the quantitative PCR and immunocytochemical experiments. CONCLUSIONS AND IMPLICATIONS: These data represent a rigorous investigation of the molecular basis of vascular transient K+ currents and implicates Kv4.3 as a major component of the channel complex.

Animals↗

PubMed2005

K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts.

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K(+) currents were recorded at depolarized potentials, and an inwardly rectifying K(+) (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K(+) concentration ([K(+)](o)) was raised, and this Kir current was blocked by 100-300 muM Ba(2+). RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [K(+)](o) influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC(3)(4), showed that 1.5 mM [K(+)](o) resulted in a hyperpolarization, whereas 20 mM [K(+)](o) produced a depolarization. Low [K(+)](o) (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [K(+)](o)). In contrast, 20 mM [K(+)](o) resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [K(+)](o) significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [K(+)](o). In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K(+) channel alpha-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions.

Animals↗

PubMed2001

Local Ca(2+) transients and distribution of BK channels and ryanodine receptors in smooth muscle cells of guinea-pig vas deferens and urinary bladder.

1. The relationship between Ca(2+) sparks spontaneously occurring at rest and local Ca(2+) transients elicited by depolarization was analysed using two-dimensional confocal Ca(2+) images of single smooth muscle cells isolated from guinea-pig vas deferens and urinary bladder. The current activation by these Ca(2+) events was also recorded simultaneously under whole-cell voltage clamp. 2. Spontaneous transient outward currents (STOCs) and Ca(2+) sparks were simultaneously detected at -40 mV in approximately 50 % of myocytes of either type. Ca(2+) sparks and corresponding STOCs occurred repetitively in several discrete sites in the subplasmalemmal area. Large conductance Ca(2+)-dependent K(+) (BK) channel density in the plasmalemma near the Ca(2+) spark sites generating STOCs was calculated to be 21 channels microm(-2). 3. When myocytes were depolarized from -60 to 0 mV, several local Ca(2+) transients were elicited within 20 ms in exactly the same peripheral sites where sparks occurred at rest. The local Ca(2+) transients often lasted over 300 ms and spread into other areas. The appearance of local Ca(2+) transients occurred synchronously with the activation of Ca(2+)-dependent K(+) current (I(K,Ca)). 4. Immunofluorescence staining of the BK channel alpha-subunit (BKalpha) revealed a spot-like pattern on the plasmalemma, in contrast to the uniform staining of voltage-dependent Ca(2+) channel alpha1C subunits along the plasmalemma. Ryanodine receptor (RyR) immunostaining also suggested punctate localization predominantly in the periphery. Double staining of BKalpha and RyRs revealed spot-like co-localization on/beneath the plasmalemma. 5. Using pipettes of relatively low resistance, inside-out patches that included both clustered BK channels at a density of over 20 channels microm(-2) and functional Ca(2+) storage sites were obtained at a low probability of approximately 5%. The averaged BK channel density was 3-4 channels microm(-2) in both types of myocyte. 6. These results support the idea that a limited number of discrete sarcoplasmic reticulum (SR) fragments in the subplasmalemmal area play key roles in the control of BK channel activity in two ways: (i) by generating Ca(2+) sparks at rest to activate STOCs and (ii) by generating Ca(2+) transients presumably triggered by sparks during an action potential to activate a large I(K,Ca) and also induce a contraction. BK channels and RyRs may co-localize densely at the junctional areas of plasmalemma and SR fragments, where Ca(2+) sparks occur to elicit STOCs.

Aniline Compounds↗

PubMed2001

Molecular cloning and expression of the novel splice variants of K(+) channel-interacting protein 2.

Two cDNAs encoding the splice variants of K(+) channel-interacting protein 2 (KChIP2) recently reported as human KChIP2 have been identified from rat, mouse, and human heart by RT-PCR. A longer variant, KChIP2L encodes a protein of 270 amino acids, which has a 50-amino-acid insertion in N-terminus in comparison with a shorter one, KChIP2S. Interestingly, both KChIP2S and KChIP2L (KChIP2S/L) but not the original KChIP2 were expressed in human heart and umbilical vein endothelial cells (HUVECs). KChIP2S transcripts but not KChIP2L were predominantly expressed in rat, mouse, and human heart and HUVECs, whereas both transcripts were expressed at low levels in other tissues such as brain, aorta, and kidney. Using chimeric proteins of green fluorescence protein (GFP) fused to the N-terminus of KChIP2S/L, the interactions between Kv4.3 and KChIP2S/L were analyzed in native and Kv4.3-expressed HEK293 cells. Specific localization of GFP-fused KChIP2S/L proteins on or near cell membrane was observed only in Kv4.3-expressed HEK293 cells.

Amino Acid Sequence↗

PubMed2001

Regional expression of the splice variants of Kv4.3 in rat brain and effects of C-terminus deletion on expressed K+ currents.

In situ hybridization and RT-PCR analyses have revealed that, among three Kv4.3 splice variants (a, b, and c) with distinct C-terminal cytoplasmic domains, the mRNA for Kv4.3a is abundant in cerebral cortex, cerebellum, olfactory bulb, and medulla oblongata, whereas the mRNA for Kv4.3c is localized mainly to hippocampus. Three new distinct splice variants of Kv4.3 (Kv4.3d, e and f), which consist of 601, 635, and 628 amino acids, respectively, and have distinct C-terminal cytoplasmic domains, were isolated from rat brain by RT-PCR. Kv4.3b, d, e and f were expressed at much lower levels in brain. Mutagenesis which removed 149 amino acids in C-terminal domain of Kv4.3a significantly slowed its rate of recovery from inactivation as measured in heterologous expression in HEK293 cells. Surprisingly, however, neither the rate of inactivation nor voltage dependence of the activation and inactivation were changed.

Amino Acid Sequence↗

PubMed2001

Comparative study of the molecular and functional expression of L-type Ca2+ channels and large-conductance, Ca2+-activated K+ channels in rabbit aorta and vas deferens smooth muscle.

The relationship between the density of ionic currents through major two channels, voltage-dependent L-type Ca2+ channels (L-type VDCC) and large-conductance, Ca2+-activated K+ channels (BKC), and the mRNA expression levels of alpha1C subunit of L-type VDCC (alpha1C) and alpha/beta subunits of BKC (alphaBK/betaBK) were compared in smooth muscle cells (SMC) of rabbit aorta and vas deferens using whole cell-voltage clamp and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The density of the currents through VDCC (ICa) and BKC (IK,Ca) at +10 mV in aortic SMC was approximately one-seventh and one-sixth respectively of that in vas deferens. Whilst application of the Ca2+ channel agonist Bay K 8644 increased ICa by 75-90% in these SMC, the increase in IK,Ca was far greater in aorta than in vas deferens. The expression of the alpha1C transcript in vas deferens was approximately 3.5 times higher than that in aorta. In contrast, expression of alphaBK/betaBK was almost identical in both tissues, indicating the dissociation of IK,Ca density from the expression levels of BKC transcripts in aorta. The results were supported by Western blot and immunocytochemical analyses using subunit-specific antibodies. The lower Ca2+ influx through VDCC in aorta activates only a very limited fraction of BKC compared with that in vas deferens. The greater expression of BKC than of VDCC in aortic SMC contributes to a strong negative feed-back mechanism that minimizes membrane depolarization and acts as a safety margin to maintain low membrane excitability.

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

PubMed2001

Principles and application of in-vitro drug pharmacokinetic simulation systems controlled by stepwise method.

The principles and application of an in-vitro pharmacokinetic simulation system controlled by a stepwise method are described. In this system, drug concentrations in a culture medium are regulated by a periodic stepwise-adjustment method. The drug concentration is increased by adding a portion of concentrated drug solution, or decreased by draining a portion of the culture medium and the subsequent addition of drug-free medium. The drug concentration is adjusted each minute with peristaltic pumps controlled by a microcomputer. Concentrations of two drugs with independent pharmacokinetics can be simulated in the same medium. An algorithm for controlling drug concentrations by a microcomputer is presented in this report. This pharmacokinetic system was successfully applied to a urinary tract infection system, in which three infection models with different severity were reproduced in vitro. The in-vitro pharmacokinetic simulation system described here could be applicable not only for evaluating the bactericidal activities of antibacterial agents but also for evaluating other categories of drugs, such as antitumor agents, based on their pharmacokinetics.

Anti-Infective Agents↗

PubMed2001

Thermoresponsive artificial extracellular matrix for tissue engineering: hyaluronic acid bioconjugated with poly(N-isopropylacrylamide) grafts.

Thermoresponsive hyaluronans (HAs) were prepared by graft polymerization of N-isopropylacrylamide (NIPAM) on HA (number-averaged molecular weight, Ma, ca. 1.5 x 10(5) and 5.0 x 10(5)) using dithiocarbamate which is a kind of iniferter (initiator, transfer agent and terminator). The degree of dithiocarbamylation (DD) as an iniferter ranged from 0.4 to 11.4% per disaccharide unit of HA. The estimated Mn of the grafted polyNIPAM (PNIPAM) ranged from approximately 5.0 x 10(3) to 8.4 x 10(4). The PNIPAM-grafted HAs (PNIPAM-HAs) were water-soluble at room temperature, while they precipitated at temperatures above approximately 34 degrees C in water. The temperature at the onset of precipitation (lower critical solution temperature: LCST) was independent of parameters of molecular architecture such as Mn of HA, degree of grafting of PNIPAM, and Mn of PNIPAM. Equilibrium transmittance of the aqueous solution above LCST decreased with an increase in both degree of grafting and Mn of PNIPAM. At physiological temperature, the PNIPAM-HA film cast from a cold solution was very wettable with water. A markedly reduced adhesion of endothelial cells to the film was observed, indicating that the PNIPAM-HA film may serve as a non-cell-adhesive matrix. Scanning electron microscopic observation appeared to differentiate supramolecular structures between rapidly freeze-dried PNIPAM-HA and nongrafted HA:PNIPAM-HA exhibited a nonuniform fibrous network, whereas the morphology of which is markedly different from that of a nongrafted HA gel exhibited a mixture of sharp needle- and platelike structures.

Acrylic Resins↗

PubMed2001

Hypersusceptibility of the Pseudomonas aeruginosa nfxB mutant to beta-lactams due to reduced expression of the ampC beta-lactamase.

The Pseudomonas aeruginosa nfxB mutant lacking mexAB-oprM showed hypersusceptibility to 9 out of 24 beta-lactams tested. This hypersusceptibility was found for the nfxB mutant lacking mexAB-oprM-mexXY (N108) but not for the nfxB mutant lacking both mexAB-oprM-mexXY and ampC. The level of the AmpC beta-lactamase induction was reduced in N108. Thus, the reduced AmpC induction must be the cause of the hypersusceptibility.

Bacterial Outer Membrane Proteins↗

PubMed2001

Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758.

Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R-102557 were examined. Variation of the length of the chain between the dioxane ring and the phenyl ring revealed that the linkage with two double bonds is the most preferable. When a cyano group was introduced to the C4 position on the benzene ring, MICs improved further. A fluorine atom was introduced to obtain CS-758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4-methylbenzonitrile using the Horner-Wadsworth-Emmons reaction.

Antifungal Agents↗

PubMed2001

Usefulness and limitation of DiBAC4(3), a voltage-sensitive fluorescent dye, for the measurement of membrane potentials regulated by recombinant large conductance Ca2+-activated K+ channels in HEK293 cells.

The usefulness of bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)), a voltage-sensitive fluorescent dye, for the measurement of membrane potentials (MPs) was evaluated in HEK293 cells, where alpha or alpha plus beta1 subunits of large conductance Ca2+-activated K+ (BK) channels were expressed (HEKBK alpha and HEKBK alphabeta). The fluorescent intensity of DiBAC4(3) was measured at various potentials under voltage-clamp for calibration to estimate the absolute MP semi-quantitatively. The resting MPs measured with DiBAC4(3) were roughly comparable to those recorded with a microelectrode; the MP in HEKBK alphabeta was 10-20 mV more negative than that in native HEK. In HEKBK alpha, the membrane hyperpolarization induced by 10 microM Evans blue, a BK channel opener, was detected with DiBAC4(3). NS-1619, another BK channel opener, induced gradual but substantial change in F/F(K) even in native HEK, while the BK channel opening effect was detected. Oscillatory membrane hyperpolarization was induced in HEKBK alphabeta by application of 10 microM acetylcholine via increase in intracellular Ca2+ concentration. The oscillatory hyperpolarization was, however, detected only as a slow hyperpolarization with DiBAC4(3). It can be concluded that relatively slow effects of BK channel modulators can be semi-quantitatively measured by use of DiBAC4(3) in HEKBK, while the limited temporal resolution and possible artifacts should be taken into account.

Barbiturates↗

PubMed2001

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

Anti-Bacterial Agents↗

PubMed2001

[In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae].

Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally. Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the lungs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections among tested drugs. MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM. MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method. MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.

Ampicillin↗

PubMed2000

Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa.

To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the following substrate specificities. All of the efflux systems extrude a wide variety of antimicrobial agent groups, i.e., quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, most penicillins (all but carbenicillin and sulbenicillin), most cephems (all but cefsulodin and ceftazidime), meropenem, and S-4661, but none of them extrude polymyxin B or imipenem. Extrusion of aminoglycosides is specific to MexXY-OprM, and extrusion of a group of the beta-lactams, i.e., carbenicillin, sulbenicillin, ceftazidime, moxalactam, and aztreonam, is specific to MexAB-OprM. Moreover, MexAB-OprM and MexCD-OprJ extrude novobiocin, cefsulodin, and flomoxef, while MexXY-OprM does not. These substrate specificities are distinct from those reported previously.

Bacterial Outer Membrane Proteins↗

PubMed2000

Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa.

To test the possibility that MexX-MexY, a new set of efflux system components, is associated with OprM and contributes to intrinsic resistance in Pseudomonas aeruginosa, we constructed a series of isogenic mutants lacking mexXY and/or mexAB and/or oprM from a laboratory strain PAO1, and examined their susceptibilities to ofloxacin, tetracycline, erythromycin, gentamicin, and streptomycin. Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested, whereas loss of MexXY from the MexAB-OprM-deficient mutant caused no change in susceptibility. Introduction of an OprM expression plasmid decreased the susceptibility of the mexAB-oprM-deficient-/mexXY-maintaining mutant, yet caused no change in the susceptibility of a mexAB-oprM- and mexXY-deficient double mutant. Immunoblot analysis using anti-MexX polyclonal rabbit serum generated against synthetic oligopeptides detected expression of MexX in the PAO1 cells grown in medium containing tetracycline, erythromycin, or gentamicin, although expression of MexX was undetectable in the cells incubated in medium without any agent. These results suggest that MexXY induced by these agents is functionally associated with spontaneously expressed OprM and contributes to the intrinsic resistance to these agents.

Anti-Bacterial Agents↗

PubMed2000

Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives.

Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidic conditions afforded a series of dioxane-triazole compounds 14-16. The antifungal activities of the compounds 14-16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.

Animals↗

PubMed2000

SK4 encodes intermediate conductance Ca2+-activated K+ channels in mouse urinary bladder smooth muscle cells.

The single channel current of intermediate conductance Ca2 +-activated K+ channel (IK channel) was measured in mouse urinary bladder myocytes (MBM), and the molecular basis of the channel was suggested to be the SK4 subtype by RT-PCR. Among Ca2+-activated K+ channel subtypes (SK2, SK3, SK4 and BK), the mRNAs of SK4 and BK were predominantly expressed in MBM. IK channel currents recorded from MBM showed: 38.7 pS slope conductance under symmetrical 140 mM K+ conditions, Ca2+-dependent activation, and blockade by charybdotoxin and econazole. These results strongly suggest that SK4 encodes IK channels in MBM.

Animals↗