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Q Li

Publications and source records attributed to Q Li.

At least 901 records · Page 50Linked to original sources
PubMed1994

LHRH-I release from quail hypothalamic slices measured by specific EIA.

A competitive enzyme immunoassay (EIA) was developed for luteinizing hormone-releasing hormone (LHRH), which measures either mammalian luteinizing hormone-releasing hormone or chicken LHRH-I (cLHRH-I). There is negligible cross-reactivity with chicken LHRH-II. Assay sensitivity is 1 pg/ml and the intra- and interassay variation are 3.4 and 10.0%, respectively. The assay was validated for measuring cLHRH-I by parallelism and quantitative recovery. Using this EIA, cLHRH-I content was measured in microdissected samples of median eminence from mature quail and chickens. Mean cLHRH-I concentrations were 1.25 +/- 0.35 and 2.10 +/- 0.25 ng/mg protein in quail and chickens, respectively. In vitro release of cLHRH-I was studied by perifusion of quail medial basal hypothalamus-preoptic area (MBH-POA) slices. Challenge with increasing concentrations of K+ resulted in significant (P < 0.05) release of cLHRH-I. The release of cLHRH-I from MBH-POA slices was also measured in response to norepinephrine (NE), epinephrine (E), and isoproterenol (ISO). Chicken LHRH-I was released in a dose-dependent manner; maximal release occurred with 10(-7) M NE, 10(-8) M E, and 10(-7) M ISO. Tissue response was optimal for experimental manipulation 6-25 hr postcollection; thereafter, the response deteriorated until 60 hr postcollection. These data extend previous studies in birds by detailed characterization of responses to neurochemical challenge and description of optimal parameters for tissue response during perifusion.

Animals↗
PubMed1994

Electrophysiological basis for the enhanced cardiac arrhythmogenic effect of isoprenaline in aged spontaneously hypertensive rats.

We used normotensive (WKY) and spontaneously hypertensive rats (SHR) of 2, 6 and 18 months of age to get insight into the mechanisms responsible for the increased incidence of ventricular arrhythmias in hypertensive heart disease. We studied: (1) isoprenaline-induced spontaneous activity in isolated papillary muscle; (2) action potential characteristics; (3) beta-adrenoceptor and A1-adenosine receptor number and affinity; and (4) intracellular cyclic AMP (cAMP) levels. The saturation binding assay was performed in enzymatically isolated ventricular myocytes using the hydrophilic antagonist 3H-CGP 12177 for beta-adrenoceptors and 3H-DPCPX for A1-adenosine receptors. cAMP was measured by a competitive binding assay in myocytes before and after exposure to isoprenaline. Intracellular action potential was recorded from papillary muscles by means of 3 M KCl-filled glass microelectrodes. The presence of isoprenaline-induced automaticity was assessed by interrupting the electrical stimulation periodically. In isolated papillary muscles, isoprenaline (10 nM) induced spontaneous activity more frequently in 18-month-old SHR (90.0%) than in 6-(25.0%, P < 0.05) and 2-month-old SHR (0%, P < 0.001). No age-related statistically significant differences in isoprenaline-induced automaticity were observed in WKY. The incidence of isoprenaline-induced automaticity was higher in 18-month-old SHR than in age-matched WKY (22.2%, P < 0.05). KD and Bmax for beta-adrenoceptors and A1-receptors were not significantly modified in different groups. cAMP levels before and after isoprenaline stimulation were significantly lower in 18-month-old SHR than in age-matched WKY. Action potential duration (APD) was markedly prolonged in both normotensive and hypertensive rats during aging. APD was significantly prolonged in 18-month-old SHR compared to the WKY. A "diastolic depolarization", caused by the presence of delayed after-depolarizations, became apparent in the oldest animals. The slope of the delayed after-depolarization was increased by isoprenaline (1-10 nM) in 18-month-old SHR and this effect was significantly greater than that observed in 18-month-old WKY (P < 0.05). In conclusion, beta-adrenergic responsiveness is enhanced in hypertensive rats during aging, resulting in a greater incidence of abnormal automaticity. This effect does not appear to be related to changes in beta-adrenoceptor or A1-receptor density or affinity; it is likely that the electrophysiological alterations may play a role in this phenomenon.

Action Potentials↗
PubMed1994

Immunohistochemical localization of endothelin-1 in non-neoplastic and neoplastic adrenal gland tissue.

Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasocontrictive properties. Biochemical studies suggest that this peptide occurs in adrenal glands, where it influences steroid hormone production. However, we have found no report of the topographical distribution of this peptide. The localization of ET-1 immunoreactivity in non-neoplastic (37 cases) and neoplastic adrenal glands (48 cases) was investigated with a sensitive immunohistochemical technique applied to routinely processed tissue specimens. ET-1 immunoreactivity was regularly seen in the cortex, especially in the zona fasciculata and to a varying extent also in the other two zones, but not in the medulla. The immunoreactive material appeared in the cytoplasm mostly in the form of vacuolar structures but also as grains. Focally, the cell membrane also showed immunoreactive staining. In the zona reticularis the immunoreactivity appeared mainly as cytoplasmic grains. Most cortical adenomas displayed numerous immunoreactive cells. The immunoreactivity in the tumour tissue appeared in the same forms as in normal cortex, but the reactive products were generally fewer in number. No obvious differences in immunostaining were seen between the aldosterone- and cortisol-producing adenomas or the non-functioning ones. Three of the ten carcinomas contained immunoreactive cells, but they were few, appearing focally and the ET-1 immunoreactive structures were seen as 'dust-like' material. The difference in immunoreactivity between the benign and the malignant cortical neoplasms may be of diagnostic value. Functionally our results support a relationship between ET-1 and steroid regulation in non-neoplastic cortical tissue.

Adrenal Gland Neoplasms↗
PubMed1994

Influence of repeated cocaine exposure on the endocrine and behavioral responses to stress in rats.

Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1-15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress-induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine.

Animals↗
PubMed1994

Presence of heat-stable hemorrhagic toxins in snake venoms.

Twenty-eight snake venoms (seven Agkistrodon venoms, six Bothrops venoms, 13 Crotalus venoms, one Sistrurus venom, and one Bitis venom) were examined for the presence of heat-stable (100 degrees C, 5 min) hemorrhagic toxins. Both heated and unheated venoms were analyzed for their protein composition by SDS-PAGE, and tested for their hemorrhagic activity in vivo in mice and for their proteolytic activity on two different substrates. Heating all venoms led to the denaturation and loss of some proteins; however, most of the venoms retained a significant number of proteins. Seventeen venoms contained more than seven proteins after heating, whereas five venoms contained only one to three proteins. All but nine of the heated venoms had substantial hemorrhagic activity, and Agkistrodon piscivorus piscivorus venom had very high activity, almost four times that of the second most hemorrhagic venom from Crotalus viridis lutosus. Most venoms, heated or unheated, had activity on the two protease substrates. Using succinylated casein as the substrate, there was a wide range of activity, and heating drastically reduced the activity of all venoms except that of Crotalus ruber and Crotalus molossus molossus. With azocoll as substrate, all but two of the unheated venoms (Crotalus adamanteus and Crotalus viridis concolor) had very high activity, whereas upon heating, all except five venoms lost essentially all of their activity. Heated venoms from snakes in the Agkistrodon genus (except for Agkistrodon blomhoffi blomhoffi, an Asian snake) retained activity on azocoll, and this activity tended to correlate better with hemorrhagic activity of the venom than did proteolytic activity on casein.

Animals↗
PubMed1994

Development of an enzyme-linked immunosorbent assay (ELISA) for identification of venoms from snakes in the Agkistrodon genus.

An enzyme-linked immunosorbent assay (ELISA) using a purified myotoxin from the venom of Agkistrodon contortrix laticintus (broad-banded copperhead) as immunogen was developed for potential use in the identification of envenomation by snakes belonging to the genus Agkistrodon native to North America. The specificity of the assay was tested using a total of 43 venom samples from snakes of diverse geographic locations. Venom samples used for cross-reactivity determination represent eight snake families including 14 species from the genus Crotalus. The assay detected venom from all Agkistrodon species tested without significant cross-reactivity with other venoms except for samples from two species of Bothrops which do not occur naturally north of Southern Mexico. The detection limit of the assay was 2 ng/ml for homologous crude venom dissolved in normal human serum. The assay was highly accurate in correlating optical densities with venom concentrations (r = 0.997). The presence of the antigen in experimental envenomations was readily detected by the assay at an i.m. injection dosage of 0.1 microgram/g. This ELISA is a promising test for identification of envenomations by species of Agkistrodon found in most of North America. It can also be used to study the kinetics of the myotoxin in experimental envenomations.

Agkistrodon↗
PubMed1994

ICV injection of the serotonin 5-HT1B agonist CP-93,129 increases the secretion of ACTH, prolactin, and renin and increases blood pressure by nonserotonergic mechanisms.

This study tested whether a new serotonin (5-HT1B) agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxy-pyrrolo[3,2-b]pyridine (CP-93,129), could be used to study the potential role of 5-HT1B receptors in the secretion of adrenocorticotropic hormone (ACTH), prolactin, and renin. CP-93,129 has a high affinity for 5-HT1B receptors but low affinity for other 5-HT receptor subtypes. In addition, CP-93,129 does not readily cross the blood-brain barrier. The secretion of ACTH, prolactin, and renin is known to be increased after activation of 5-HT receptors. ICV injections of CP-93,129 (100 micrograms/kg) increased the plasma concentrations of ACTH, prolactin, and renin. CP-93,129 also increased blood pressure and reduced heart rate. To determine whether these effects of CP-93,129 are centrally mediated, we compared them with IP injection of the same dose of CP-93,129. IP-injected CP-93,129 did not alter blood pressure or heart rate and did not elevate plasma prolactin and renin concentrations. To determine whether 5-HT1B receptors mediate the central effects of CP-93,129, rats were pretreated with the 5-HT antagonists l-propranolol or metergoline prior to ICV injections of doses of CP-93,129 (0-100 micrograms/kg). The 5-HT1A/1B/2A/2C antagonist metergoline (0.5 mg/kg, IP) failed to inhibit the CP-93,129-induced elevation of ACTH, prolactin, or renin concentrations. In contrast, the 5-HT1A/1B/beta antagonist l-propranolol (20 micrograms/kg, ICV) inhibited the renin but not the ACTH or prolactin responses to ICV CP-93,129.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Cocaine-induced deficits in ACTH and corticosterone responses in female rat progeny.

The objective of this study was to determine whether prenatal exposure to cocaine could produce functional changes in central serotonergic systems mediating neuroendocrine responses in female progeny. Pregnant rats were administered either saline or (-) cocaine (15 mg/kg, SC, b.i.d.) from gestational day 13-20. Progeny were fostered to nontreated lactating dams at birth. Central serotonergic function was determined by the ability of a serotonin releaser, p-chloroamphetamine (PCA), to stimulate plasma adrenocorticotropin (ACTH), corticosterone, and renin secretion in female progeny at postnatal day (PD) 30. Prenatal cocaine did not alter basal levels of ACTH, corticosterone, or renin. In contrast, ACTH and corticosterone responses to the 5-HT releaser PCA were significantly attenuated (-28% to 43%) in cocaine progeny, while the renin response to PCA was unaffected. These data suggest that cocaine administration during pregnancy can produce long-term selective alterations in neuroendocrine responses mediated by central serotonergic systems in prepubescent female progeny.

Adrenocorticotropic Hormone↗
PubMed1994

Novel Ca(2+)-ATPase inhibitors from the dried root tubers of Polygonum Multiflorum.

The MeOH extract of the dried root tubers of Polygonum multiflorum yielded three bioactive compounds with an inhibitory activity on calmodulin-depleted erythrocyte calcium-dependent ATPase. These compounds were identified as E-2,3,5,4'-tetrahydroxystilbene 2-O-beta-D-glucopyranoside [2] (IC50 = 240 microM) and cis- and trans-E-3-butylidene-4,5,6,7-tetrahydro-6,7-dihydroxy-1(3H)- isobenzofuranone [3 and 4](IC50 = 160 and 260 microM, respectively). E-2,4,6,4'-Tetrahydroxystilbene 2-O-beta-D-glucopyranoside [1] was also isolated but was found to have no inhibitory effect on the enzyme.

Australia↗
PubMed1994

Ionic basis of action potential prolongation of hypertrophied cardiac myocytes isolated from hypertensive rats of different ages.

OBJECTIVE: The aim was to determine the ionic basis of action potential lengthening associated with cardiac hypertrophy. METHODS: Action potentials and ionic currents of left ventricular myocytes isolated from normal and hypertrophied hearts were recorded with patch pipettes. Since cardiac hypertrophy is a time dependent process, myocytes isolated from hearts of spontaneously hypertensive rats (SHR) of different ages (3 and 18 months old) were compared with those of age matched normotensive controls (Wistar Kyoto rats, WKY). RESULTS: Membrane capacitance, an index of cell size, was significantly higher in SHR than WKY. The degree of action potential prolongation was independently correlated with hypertension and its duration, resulting in a statistically significant lengthening of action potential in 18 month old SHR compared to age matched WKY and to 3 month old SHR. ICa,L density was not significantly modified in hypertrophied myocytes compared to normal controls. Depolarising steps positive to -40 mV activated an outward current, which was composed of both transient (ItO) and maintained components (Ilate) and played a major role in controlling repolarisation in rat ventricular myocytes. Ito density was significantly reduced in SHR myocytes compared to age matched WKY and was also smaller in 18 month old compared to 3 month old SHR. Ilate was not statistically different in 3 and 18 month old SHR and WKY. Current-voltage relationships for IK1 were completely superimposable in all groups. CONCLUSIONS: Prolongation of action potential in the hypertrophied heart of SHR is due to specific alterations in the repolarising potassium current Ito. The phenomenon is directly related to the duration of hypertension.

Action Potentials↗
PubMed1994

Estradiol and androgen modulate chicken luteinizing hormone-releasing hormone-I release in vitro.

Hypothalamic slices (1 mm) including medial basal hypothalamus and preoptic areas (MBH-POA) were taken from adult male Japanese quail, placed in a short-term perifusion system, and exposed to estradiol or androgen. Release of chicken LHRH-I (cLHRH-I) was measured by an enzyme immunoassay specific for cLHRH-I. In separate experiments, MBH-POA slices were exposed short-term to 5 alpha-dihydrotestosterone (5 alpha-DHT, 10(-7) M) and testosterone (T, 10(-7) M), and short- or long-term to 17 beta estradiol (E2, 10(-9) M). Release of both basal and stimulated cLHRH-I (15-min exposure to 10(-6) M norepinephrine [NE]) was monitored. Basal cLHRH-I release during perfusion was episodic throughout the experimental periods. During no treatment, there was a mean (+/- SEM) pulse interval of 21.27 +/- 1.03 min, pulse duration of 13.98 +/- 0.59 min, pulse duration of 13.98 +/- 0.59 min, pulse amplitude of 4.12 +/- 0.13 pg/5 min, and pulse frequency of 2.93 +/- 0.12/h. Mean cLHRH-I pulse amplitude significantly (p < 0.05) increased with challenge by NE to 25.03 +/- 3.09 pg/5 min. Short-term E2 exposure significantly (p < 0.01) potentiated NE-induced cLHRH-I release. Neither T nor 5 alpha-DHT affected baseline or NE-stimulated cLHRH-1 release. Pretreatment with E2 (10(-9) M) for 14 h in static culture before perifusion significantly (p < 0.05) reduced the NE-induced cLHRH-I release. These results suggest that a hypothalamic LHRH-I pulse-generating mechanism is located within the MBH-POA. Further, these data provide evidence for E2 modulation of cLHRH-I release, which varies with exposure.

Androgens↗
PubMed1994

Effects of the new phosphodiesterase-III inhibitor R80122 on contractility and calcium current in human cardiac tissue.

The selective phosphodiesterase III (PDE-III) inhibitor R80122 ((E)-N-cyclohexal-N-methyl-2-[[[phenyl-(1,2,3,5- tetrahydro-2-oxoimidazo-[2,1b]-quinazolin-7-yl)-methylene]-a mino]-oxy]-acetamide) has been reported to possess greater cardiotonic potency and less side effects than the standard compounds milrinone or enoximone. To characterize this new compound further, we investigated the effects of R80122 on force of contraction (Fc) and calcium current (ICa) in human right atrium (HRA) and human left ventricle (HLV) with reference to the nonselective PDE-inhibitor IBMX (3-isobutyl-1-methylxanthine). With "late" exposure (300- to 330-min equilibration) of human atrial trabeculae, R80122 (3 microM) increased Fc by 60 +/- 11%; log EC50 was -6.2 +/- 0.1. R80122 (3 microM) induced a relative leftward shift of forskolin concentration-response curves by 0.34 log units; the respective value for IBMX (20 microM) was 0.46. A positive inotropic effect of R80122 was also shown in guinea pig papillary muscles. ICa was measured in voltage-clamped isolated myocytes of human right atrial and left ventricular (LV) tissue, and, for comparison, guinea pig ventricle. With clamp steps from -40 to +5 mV, R80122 (3 microM) increased peak ICa from 3.1 +/- 0.2 to 5.4 +/- 0.3 pA/pF in HRA cells, from 2.9 +/- 0.4 to 5.1 +/- 0.6 pA/pF in HLV cells, and from 4.4 +/- 0.3 to 6.6 +/- 0.5 pA/pF in guinea pig myocytes. IBMX 20 microM increased ICa to a greater extent. Washout or addition of carbachol 10 microM partially reversed the effect of R80122. Voltage dependence, inactivation time course, and steady-state inactivation of ICa were little changed by either compound. Stimulation of Ca2+ influx by L-type Ca2+ channels contributes to the positive inotropic effect of the selective PDE-III inhibitor R80122.

1-Methyl-3-isobutylxanthine↗
PubMed1994

The protective effect of glycine in cisplatin nephrotoxicity: inhibition with NG-nitro-L-arginine methyl ester.

The effect of glycine on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin was investigated in the rat. Cisplatin (6.0 mg kg-1, i.v.) injection in anaesthetized rats produced, over a period of 2 h, falls of approximately 50% in renal blood flow (RBF) and the clearance of [3H]inulin (CLIN), effects which were prevented by co-administration of glycine (1.0 g kg-1). Infusion of the nitric oxide (NO) synthase-inhibitor NG-nitro-L-arginine methyl ester, L-NAME (10 micrograms min-1 kg-1, i.v.), abolished glycine's ability to maintain RBF in cisplatin-injected rats whilst partially inhibiting the ability of glycine to preserve CLIN. Treatment of cisplatin-injected rats with glycine (1.0 g kg-1, i.v.) significantly ameliorated the nephrotoxic effects of cisplatin (6.0 mg kg-1) as judged by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CLIN and the clearance of [14C]p-aminohippurate. Administration of L-NAME (1.0 mg kg-1, i.v.) to rats which received cisplatin and glycine significantly inhibited the reno-protective effect of glycine. However, L-NAME administration to rats which were treated only with cisplatin did not result in any potentiation of cisplatin nephrotoxicity. The findings of this study suggest that glycine can block the acute falls in RBF and CIN produced by cisplatin by a mechanism which involves the production of NO. Furthermore, the results indicate that these renal haemodynamic actions of glycine are responsible, at least in part, for the ability of this amino acid to ameliorate cisplatin nephrotoxicity.

Analysis of Variance↗
PubMed1994

Diuretic effect of NG-nitro-L-arginine methyl ester in the rat.

Intravenous infusion of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, L-NAME (10 micrograms kg-1 min-1), to anaesthetized rats produced a diuresis and natriuresis. By contrast, infusion of the same dose of NG-nitro-D-arginine methyl ester had no effect on either urine output or sodium excretion. The effects of L-NAME were first evident 120 min after the start of infusion and by 170 min a fivefold increase in urine volume and sodium excretion was recorded. L-NAME also produced a transient fall in inulin clearance and a persistent decline in renal blood flow. These renal effects of L-NAME were associated with a gradual elevation of mean arterial blood pressure, although this only attained statistical significance, in comparison with saline-infused animals, 170 min after the start of infusion. The findings indicate the diuresis and natriuresis evoked by L-NAME in the rat is a result of a direct tubular action together with a pressure diuresis.

Animals↗
PubMed1994

Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature.

Antisera were raised against peptide sequences that are normally internal in the poliovirus virion. These antisera contain neutralizing activity, but this neutralizing activity is dependent on coincubation of the virus and antisera at 37 degrees C. Immunoprecipitation analyses demonstrate that the neutralization is due to exposure of these normally internal sequences at 37 degrees C and subsequent antibody binding. Exposure of these sequences is reversible. These data demonstrate that the poliovirus particle is a dynamic entity that is capable of undergoing conformational alterations at physiological temperatures. This conformational flexibility provides an explanation for earlier observations of virus neutralization by antibodies to internal epitopes which can be accommodated within the framework of existing models for antibody-mediated neutralization of viral infectivity. Analogies between the sequences which are reversibly exposed at 37 degrees C with those which are irreversibly exposed upon receptor binding suggest that the observed conformational dynamics also may play a role in cell entry.

Antibodies, Viral↗
PubMed1994

Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element.

We have analyzed the expression of human gamma-globin genes during development in F2 progeny of transgenic mice carrying two types of constructs. In the first type, gamma-globin genes were linked individually to large (approximately 4-kb) sequence fragments spanning locus control region (LCR) hypersensitive site 2 (HS2) or HS3. These LCR fragments contained not only the core HS elements but also extensive evolutionarily conserved flanking sequences. The second type of construct contained tandem gamma- and beta-globin genes linked to identical HS2 or HS3 fragments. We show that gamma-globin expression in transgenic mice carrying HS2 gamma or HS3 gamma constructs is highly sensitive to position effects and that such effects override the cis regulatory elements present in these constructs to produce markedly different developmental patterns of gamma-globin expression in lines carrying the same transgene. In contrast, gamma-globin expression in both HS2 gamma beta and HS3 gamma beta mice is sheltered from position effects and the developmental patterns of gamma-globin expression in lines carrying the same transgene are identical and display stage-specific regulation. The results suggest that cis regulatory sequences required for proper developmental control of fetal globin expression in the presence of an LCR element reside downstream from the gamma genes.

Age Factors↗
PubMed1994

Effects of myocardial hypertrophy on transient outward current.

In the one-clip, two-kidney model of hypertensive rat, a gradual chronic pressure overload is imposed on the heart. Myocardial hypertrophy resulting from such pressure overload is associated with an increased but slower inactivating L-type calcium current and prolongation of action potential duration. Voltage clamp experiments in a variety of excitable tissues indicate that a 4-aminopyridine-sensitive transient outward current (Ito) plays an important role in regulating the action potential duration. Accordingly, we studied Ito in single adult cardiac myocytes enzymatically isolated from hypertrophied left ventricles of the renovascular hypertensive (HBP) rat hearts using the whole cell patch-clamp method. The current densities (normalized to cell capacitative surface area) measured at the early transient peak Ito, at the steady state, and as the difference between the transient peak and the steady state were larger in HBP cells (n = 23) than in control (Ctrl) cells (n = 20) (P < 0.05). There was no difference in the Ito reversal potential between Ctrl (-60.9 +/- 1.9 mV, mean +/- SE; n = 16) and HBP (-63.7 +/- 2.6 mV; n = 19) cells. The observed increase in Ito amplitude was not due to an increase in the number of channels available for activation or in the fraction of channels activated because there were no statistical differences in the membrane potential at which one-half of the Ito channels are activated (V0.5) for the steady-state activation and inactivation curves between Ctrl and HBP cells. The time course of inactivation of Ito was described by a double-exponential function.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗