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S D Koh

Publications and source records attributed to S D Koh.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles.

Kv2.2, homologous to the shab family of Drosophila voltage-gated K+ channels, was isolated from human and canine colonic circular smooth muscle-derived mRNA. Northern hybridization analysis performed on RNA prepared from tissues and RT-PCR performed on RNA isolated from dispersed and selected smooth muscle cells demonstrate that Kv2.2 is expressed in smooth muscle cells found in all regions of the canine gastrointestinal (GI) tract and in several vascular tissues. Injection of Kv2.2 mRNA into Xenopus oocytes resulted in the expression of a slowly activating K+ current (time to half maximum current, 97 +/- 8.6 ms) mediated by 15 pS (symmetrical K+) single channels. The current was inhibited by tetraethylammonium (IC50 = 2.6 mM), 4-aminopyridine (IC50 = 1.5 mM at +20 mV), and quinine (IC50 = 13.7 microM) and was insensitive to charybdotoxin. Low concentrations of quinine (1 microM) were used to preferentially block the slow component of the delayed rectifier current in native colonic myocytes. These data suggest that Kv2.2 may contribute to this current in native GI smooth muscle cells.

4-Aminopyridine↗
PubMed1997

Small-conductance Ca(2+)-dependent K+ channels activated by ATP in murine colonic smooth muscle.

The patch-clamp technique was used to determine the ionic conductances activated by ATP in murine colonic smooth muscle cells. Extracellular ATP, UTP, and 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) increased outward currents in cells with amphotericin B-perforated patches. ATP (0.5-1 mM) did not affect whole cell currents of cells dialyzed with solutions containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Apamin (3 x 10(-7) M) reduced the outward current activated by ATP by 32 +/- 5%. Single channel recordings from cell-attached patches showed that ATP, UTP, and 2-MeS-ATP increased the open probability of small-conductance, Ca(2+)-dependent K+ channels with a slope conductance of 5.3 +/- 0.02 pS. Caffeine (500 microM) enhanced the open probability of the small-conductance K+ channels, and ATP had no effect after caffeine. Pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid tetrasodium (PPADS, 10(-4) M), a nonselective P2 receptor antagonist, prevented the increase in open probability caused by ATP and 2-MeS-ATP. PPADS had no effect on the response to caffeine. ATP-induced hyperpolarization in the murine colon may be mediated by P2y-induced release of Ca2+ from intracellular stores and activation of the 5.3-pS Ca(2+)-activated K+ channels.

Adenosine Triphosphate↗
PubMed1996

Activation of delayed rectifier potassium channels in canine proximal colon by vasoactive intestinal peptide.

1. Vasoactive intestinal peptide (VIP) inhibits phasic contractions and tone of gastrointestinal smooth muscles. This study examines electrical mechanisms that may mediate the inhibitory actions of VIP. 2. Electrical slow waves were recorded from canine proximal colon circular muscles. VIP (0.1 microM) decreased basal slow wave frequency but had no effect on amplitude or duration. When slow waves were enhanced with Bay K 8644 (1 microM), VIP decreased slow wave duration and inhibited contractions. 3. VIP inhibited slow waves and phasic contractions stimulated by tetraethylammonium chloride (TEA; 10 mM), but did not significantly reduce events stimulated by 4-amino-pyridine (4-AP; 10 mM). 4. Whole-cell outward currents were recorded from isolated myocytes, using the amphotericin B perforated patch technique. VIP (1 microM) increased charybdotoxin-insensitive outward currents. 5. Single voltage-dependent K+ channels were recorded in cell-attached patches. VIP increased reversibly the open probability, mean open time and mean burst duration of 4-AP-sensitive, charybdotoxin-insensitive K+ channels (KDR1). Two additional 4-AP- and charybdotoxin-insensitive K+ channels (approximately 90 pS and < 4 pS) were also observed in these patches, but were not significantly affected by VIP. 6. In summary, the effects of VIP on electrical slow waves may be due, in part, to activation of 4-AP-sensitive, 'delayed rectifier' K+ channels. Activation of these channels may contribute to premature slow wave repolarization, reduced Ca2+ entry, and inhibition of contractile force.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Regulation of smooth muscle delayed rectifier K+ channels by protein kinase A.

We identified voltage-activated K+ channels in freshly dispersed smooth muscle cells from the circular layer of the canine colon in patch-clamp experiments using 200 nM charybdotoxin to suppress 270-pS Ca2+-activated K+ channels (BK channels). Three channel types were distinguished in symmetrical 140 mM KCl solutions: 19.5 +/- 1.7 pS channels (KDR1), 90.6 +/- 5.4 pS channels (KDR2) and 149 +/- 4 pS intermediate-conductance Ca2+-activated K+ channels (IK channels). All three types showed an increase in open probability with membrane depolarization. Ensemble average current from KDR1 channels inactivated with a time constant of 1.7 +/- 0.1 s at +60 mV test potential, while KDR2 and IK channels did not show inactivation. IK channels were activated by free cytoplasmic [Ca2+] (10(-6 )M) but were insensitive to 4-aminopyridine (4-AP, 10 mM) and intracellular tetraethylammonium (TEA, 1 mM). KDR1 channels were sensitive to 4-AP (10 mM) and intracellular TEA (1-10 mM) but not to Ca2+. KDR2 channels did not have a consistent pharmacological profile, suggesting that this class may be comprised of several subtypes. At +40 mV membrane potential, the catalytic subunit of protein kinase A (PKA) increased the open probability of KDR1 channels 3.4-fold and of KDR2 channels 3.9-fold, but had no effect on IK channels. In the absence of Mg-ATP, PKA did not affect channel open probabilities. At physiological membrane potentials (-60 mV) only openings of KDR1 channels could be induced by PKA, suggesting that these 4-AP-sensitive 20-pS K+ channels are primarily responsible for the cAMP-mediated hyperpolarization of colonic smooth muscle cells.

4-Aminopyridine↗
PubMed1996

Modulation of Ca2+ current in canine colonic myocytes by cyclic nucleotide-dependent mechanisms.

Regulation of Ca2+ currents by cyclic nucleotide-dependent mechanisms was studied in circular muscle cells isolated from canine proximal colon. Whole cell Ca2+ currents were recorded at 32 degrees C with the use of amphotericin B-perforated patches. The effects of several agents known to increase levels of adenosine 3',5'-cyclic monophosphate (cAMP) were tested. Vasoactive intestinal peptide (VIP) and isoproterenol (10(-7) to 10(-5) M) increased Ca2+ current in a concentration-dependent manner. Forskolin (10(-7) M) and dibutyryl cAMP (10(-6) to 10(-5) M) also increased Ca2+ current. Higher concentrations of forskolin (10(-6) to 10(-5) M) caused inhibition of Ca2+ current. Low concentrations (10(-5) to 10(-7) M) of dibutyryl cAMP or 8-bromo-cAMP caused concentration-dependent enhancement in Ca2+ current, and these effects were reversible on washout of the cAMP analogues. When the concentration of cAMP analogues was increased (10(-3) to 10(-4) M), we observed inhibition of Ca2+ current similar to the effects of forskolin. Membrane-permeable analogues of guanosine 3',5'-cyclic monophosphate produced exclusively inhibitory effects. The nonspecific protein kinase inhibitor H-7 (up to 60 microM) failed to block the effects of VIP, isoproterenol, and forskolin, and it produced inhibitory effects on Ca2+ current, independent of agonist stimulation. The data suggest that low levels of cAMP may, via phosphorylation by protein kinase A, enhance L-type Ca2+ current, but higher concentrations of cAMP may "cross over" and activate protein kinase G. Phosphorylation by protein kinase G appears to produce a dominant inhibition of Ca2+ current.

Adrenergic alpha-Agonists↗
PubMed1995

Nitric oxide activates multiple potassium channels in canine colonic smooth muscle.

1. Nitric oxide (NO), an inhibitory neurotransmitter released from peripheral neurones, hyperpolarizes smooth muscle cells and inhibits contraction. The mechanism of this hyperpolarization is unknown. 2. We have identified three classes of K+ channels activated by NO and NO donors in colonic smooth muscle cells. NO and NO donors increased the open probability of 80 pS channels (KNO1), very small channels (< 4 pS, KNO2), and 270 pS Ca(2+)-activated K+ channels (BK channels) in cell-attached patches. 3. Dibutyryl cGMP and 8-bromo cGMP also increased the open probability of KNO1 and KNO2 in cell-attached patches. 4. In excised patches of membrane, direct application of NO or the NO donor, S-nitroso-N-acetyl penicillamine (SNAP), increased the open probability of KNO1 and KNO2, but cGMP or dibutyryl cGMP had no effect. SNAP had no effect on the open probability of BK channels in excised patches. 5. The reducing agent dithiothreitol and the alkylating agent N-ethylmaleimide blocked NO-induced channel openings. 6. In summary, the hyperpolarization response to NO in smooth muscles may be mediated by multiple K+ channels. At least two of these classes of channels may be activated by dual pathways involving direct activation by NO and cGMP-mediated mechanisms.

Animals↗
PubMed1983

Memory scanning and retrieval in affective disorders.

Previous studies have consistently demonstrated unimpaired memory scanning and retrieval in schizophrenic patients. Using the choice-reaction time paradigm, this study assessed the speed of short-term memory processing for pictorial information in both unipolar and bipolar depressives by comparing it with that of schizophrenics. It was found that the processing rate is comparable between depressives and schizophrenics, between unipolar and bipolar depressives, and between depressives on medication and those not on medication. It was concluded, therefore, that the short-term memory scanning and retrieval processes are not impaired in depressive patients. The results further suggested that the depressives' slowness often found in simple reaction time tasks may result from a dysfunction in their stimulus encoding and/or response execution rather than in the central information-identification process.

Adult↗
PubMed1981

Affective memory and schizophrenic anhedonia.

Two experiments attempted to isolate and measure schizophrenic anhedonia as it is reflected in the mnemonic processing of affectively laden stimuli. In the first experiment, subjects were required to sort a list of words repeatedly, each in terms of pleasantness, until a consistent sorting was achieved. Then, they were unexpectedly asked to recall the list. Schizophrenics' total recall was comparable to that of normals; but while normals recalled significantly more pleasant than unpleasant words (a Pollyanna tendency), such differential recall was absent in schizophrenics (anhedonia). These results were complicated, however, by the intrusion of semantic variables into the affective processing. In the second experiment, human faces were used to minimize semantic intrusions. Subjects were induced to encode photographs of faces in the context of favorable-unfavorable personality traits, and their recognition memory for these faces was subsequently tested. In spite of comparable overall performance, normals recognized significantly more favorably than unfavorably encoded faces, and such asymmetric recognition was absent in schizophrenics. Furthermore, a significant Group by Affect interaction emerged. The results were taken as evidence of schizophrenic anhedonia and normals' Pollyanna tendency. Nonschizophrenics also served as controls but their results were equivocal. Several problems which may be typical in the experimental investigation of affect were discussed.

Adolescent↗
PubMed1981

Memory processing with lithium carbonate.

The effect of lithium carbonate treatment on the memory processing of manic-depressive patients was assessed in three memory tasks. The results suggested that memory performance and the underlying organizational processes are not adversely affected by lithium treatment.

Bipolar Disorder↗
PubMed1976

Short term memory for numerousness in schizophrenic young adults.

The short term memory of schizophrenics for random dot patterns was examined by a delayed comparison procedure. In experiment 1, the 10 schizophrenics and 10 normals compared a fixed dot pattern (standard) with a variable dot pattern (compairson) appearing 2 or 8 seconds later and decided whether the comparison stimulus had "more" or "less" dots than the standard. Memory strength, indexed by the d' value of signal-detection theory, showed neither group difference nor decay over time. In experiment 2, the interstimulus interval was filled with an unjudged dot pattern (storage interference), and the standard stimulus followed the variable comparison stimulus (encoding difficulty). The memory strength of 17 schizophrenics and 17 normals was severely impaired, and their memory strength weakened over time, but again, no group differences were found. In both experiments, the two groups showed a strong bias (beta) in underestimating the first (to-be-remembered) stimulus. It was concluded that schizophrenics' short term perceptual memory for nonverbal stimuli remains good.

Adolescent↗
PubMed1976

Postpsychotic state, convalescent environment, and therapeutic relationship in schizophrenic outcome.

The authors evaluated the following variables in the 2-3-year outcomes of 30 schizophrenic patients: the acute/chronic dichotomy, the presence of a postpsychotic regressive state, the quality of the convalescent environment, and the formation of a therapeutic relationship. They found that the presence of a postpsychotic regressive state was not associated with either good or poor short-term outcome; that the diagnosis of acute schizophrenia was almost invariably followed by good outcome, but a diagnosis of chronic schizophrenia had little predictive value; and that a favorable convalescent environment and the presence of a therapeutic relationship were signigicantly associated with good outcome.

Acute Disease↗