Biomedical subjects

Y Takata

Publications and source records attributed to Y Takata.

At least 145 records · Page 8Linked to original sources

PubMed1994

Doxazosin withdrawal and ambulatory blood pressure monitoring in normotensive subjects.

The effect of doxazosin withdrawal on normotensive subjects was examined by ambulatory blood pressure monitoring (ABPM) during twenty-four hours. Eight normotensive volunteers were treated with doxazosin for four weeks. ABPM was done the day before withdrawal and on the second and seventh days after withdrawal. The average systolic and diastolic BP were not altered by doxazosin withdrawal either on day 2 or day 7, but pulse rate (PR) decreased on day 2 and day 7. Daytime PR decreased on day 2, but both daytime and nighttime PR decreased on day 7. On withdrawal of doxazosin, the plasma norepinephrine concentration decreased and the plasma renin activity tended to decrease. Neither overshooting hypertension nor cardiovascular event was related to doxazosin withdrawal was observed. It is concluded that, in normotensive subjects, discontinuation of doxazosin may result in bradycardia without hypotension or signs of withdrawal syndrome.

Adult↗

PubMed1994

Doxazosin and 48-hour ambulatory blood pressure monitoring in normotensive subjects.

The effect of long-term doxazosin treatment on normotensive subjects was evaluated by 48-hour ambulatory blood pressure (BP) monitoring (ABPM). Eight normotensive volunteers were given 1 mg of doxazosin per day, and the dose was titrated every week up to 8 mg/day. The 48-hour ABPM, using a noninvasive device, was performed before treatment and during the 4th week of treatment. Doxazosin did not decrease the average 48-hour systolic BP, but diastolic BP decreased slightly (3 mmHg). This slight decrease in 48-hour diastolic BP was observed during the daytime. The 48-hour pulse rate (PR) was clearly elevated by doxazosin, which was attributed to tachycardia at night. Thus, the present study using 48-hour ABPM indicated that long-term doxazosin treatment may result in only slight daytime hypotension with apparent nighttime tachycardia in normotensive subjects.

Adult↗

PubMed1994

Crossover comparison of the effects of enalapril and captopril on potassium homeostasis in patients with mild hypertension.

The effects of two types of angiotensin converting enzyme (ACE) inhibitors, enalapril (long-acting) and captopril (short-acting), on serum electrolytes and circadian rhythm of urinary electrolyte excretions were compared in relation to aldosterone status in patients with essential hypertension and normal renal function. Enalapril (5 mg once daily) and captopril (12.5 mg t.i.d.) were administered to 11 patients for 1 week each in a crossover fashion. Blood sampling in the early morning and 4-hour split urinary sampling for 24 hours were performed on the last day of control and each treatment periods. Enalapril and captopril significantly reduced blood pressure to similar levels. Enalapril but not captopril significantly inhibited plasma aldosterone concentration and urinary aldosterone excretion. Neither drug apparently altered serum or urinary Na levels. Both drugs significantly decreased urinary K excretion (p < 0.05, control: 44 +/- 4 mEq/day, captopril: 39 +/- 2 mEq/day, enalapril: 39 +/- 2 mEq/day; mean +/- SEM), but did not significantly alter serum K level (control: 4.1 +/- 0.1 mEq/l, captopril 4.2 +/- 0.2 mEq/l, enalapril 4.3 +/- 0.1 mEq/l). The circadian rhythm (acrophase) of urinary K excretion was not affected by either drug, while the amplitude was decreased by both, as assessed by the cosinor method. In summary, although enalapril caused more sustained inhibition of aldosterone secretion compared with captopril, both drugs showed similar effects on the K homeostasis in patients with mild essential hypertension.

Aldosterone↗

PubMed1994

Hypertension and ageing impair acetylcholine-induced vasodilation in rats.

OBJECTIVE: To investigate the influence of hypertension and ageing on the in vivo effect of acetylcholine on blood pressure and regional vascular conductance and the inhibitory effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on the effects of acetylcholine. METHODS: Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 3-4, 7-8 and 20-26 months, were anaesthetized with pentobarbital. After sino-aortic denervation, regional blood flow in the left common carotid, superior mesenteric, right renal and right femoral arteries was measured with pulsed Doppler flowmeters. After pretreatment with indomethacin (2 mg/kg intravenously), bolus injections of acetylcholine (0.03, 0.1 and 0.3 microgram/kg intravenously) were given with or without L-NMMA (20 mg/kg intravenously). RESULTS: Dose-dependent hypotensive responses to acetylcholine were significantly smaller in SHR than in WKY rats in each age group. Ageing reduced the hypotensive effect of acetylcholine in both SHR and WKY rats. In rats aged 3-4 and 7-8 months acetylcholine-induced increases in regional vascular conductances were significantly smaller in SHR than in WKY rats. Ageing reduced acetylcholine-induced increases in regional vascular conductances in WKY rats. L-NMMA had little effect on the responses to acetylcholine in both SHR and WKY rats. Sodium nitroprusside had similar effects in SHR and WKY rats and in age groups within each strain. CONCLUSION: The in vivo vasodilatory action of acetylcholine, which appeared to be partly independent of nitric oxide, was impaired by hypertension and age.

Acetylcholine↗

PubMed1994

Characterization of the alpha-1 adrenoceptors in the mesenteric vasculature from deoxycorticosterone-salt hypertensive rats: studies on vasoconstriction, radioligand binding and postreceptor events.

The vasoconstrictor responses to alpha-1 adrenoceptor agonists, binding behavior of alpha-1 adrenoceptors and postreceptor events in the mesenteric vasculature from deoxycorticosterone acetate-salt hypertensive rats were studied. The reactivity of perfused mesenteric artery to norepinephrine (NE) and phenylephrine, but not KCl, was enhanced significantly in the hypertensive rats compared with control rats. Prazosin antagonized the pressor response to NE more effectively in the hypertension than in the control. [3H]Prazosin binding was saturable and a single class of specific sites. Scatchard analysis revealed that the dissociation constant for [3H]prazosin was lower and the maximum binding capacity was greater in the hypertensive rats than in the control rats. The NE-stimulated phosphatidylinositol hydrolysis, estimated by measuring inositol 1,4,5-triphosphate (IP3) accumulation, was greater in the hypertensive rat artery compared with the control one. The IP3-induced contraction in the beta-escin-treated mesenteric large resistance vessel was smaller in the hypertensive rats. The vasoconstrictor response to phorbol 12,13-dibutyrate of the perfused mesenteric artery was larger in the hypertensive animals than in the control. Staurosporine antagonized the phorbol 12,13-dibutyrate-induced vasoconstriction in preparations from both rats. These results suggest that the increases in the number and affinity of alpha-1 adrenoceptors may result in an enhanced phosphatidylinositol hydrolysis accounting for an increased vascular reactivity to alpha-1 adrenoceptor agonists in deoxycorticosterone acetate-salt hypertensive rats. Furthermore, the enhancement of vasoconstrictor mechanism mediated by protein kinase C pathway may also contribute to vascular hyper-reactivity to NE, whereas the decreased IP3-induced contraction may function to minimize the hyper-reactivity observed in this model of experimental hypertension.

Animals↗

PubMed1993

Importance of Asp1191 for tyrosine kinase activity of the insulin receptor: functional difference of universally conserved Asp between tyrosine kinase and c-AMP dependent serine/threonine protein kinase.

Asp1191 of the tyrosine kinase domain in the insulin receptor is located in the almost perfectly conserved Ser-Asp-X-Trp motif of all tyrosine kinases, and the function of the motif has not been clarified. In this motif, Asp1191 is universally conserved in all protein kinases and corresponds to Asp220 in catalytic subunit of c-AMP dependent protein kinase. However, while other universally conserved amino acid residues are involved in catalysis, only Asp220 is not. To determine whether this motif was not also involved in catalysis, Asp1191 was replaced either by alanine, asparagine, or glutamic acid and Met1192 was replaced by valine. Asp1191-->Ala, Asn or Glu receptor lacked tyrosine kinase activity, while Met1192-->Val receptor showed normal kinase activity. These mutant receptors had no effect on insulin binding. These results suggested that the universally conserved Asp1191 in all protein kinases, which was not required for catalytic action of c-AMP dependent protein kinase, was essential for the tyrosine kinase activity of the insulin receptor.

Amino Acid Sequence↗

PubMed1993

Insulin activates p21Ras and guanine nucleotide releasing factor in cells expressing wild type and mutant insulin receptors.

Insulin stimulates the formation of p21RasGTP in Rat-1 fibroblasts overexpressing wild type (HIRc) or mutant (delta CT and Y/F2) insulin receptors. Maximal insulin effect was observed at 7 min in Y/F2 cells, at 10 min in delta CT cells, and at 15 min in HIRc cells. Mutant insulin receptors which display enhanced mitogenic signaling properties stimulated p21Ras.GTP formation to a greater extent than wild type receptors. The amount of p21Ras was not affected by insulin (Western blotting). Tyrosine kinase inhibitor, Lavendustin A (10 nM), completely prevented insulin-induced activation of p21Ras in all cell lines. Insulin did not lead to GAP phosphorylation, or a change in cellular GAP activity, but did result in marked stimulation of Ras guanine nucleotide releasing factor (GRF) activity (by 48% in HIRc, 71% in delta CT, and 120% in Y/F2 cells). These results indicated that p21Ras.GTP is an important signaling molecule in insulin's mitogenic pathway, but may not participate in metabolic signaling and that insulin's stimulatory effects on p21Ras.GTP formation are mediated through Ras GRF.

Animals↗

PubMed1993

The insulin receptor C-terminus is involved in regulation of the receptor kinase activity.

During the insulin receptor activation process, ligand binding and autophosphorylation induce two distinct conformational changes in the C-terminal domain of the receptor beta-subunit. To analyze the role of this domain and the involvement of the C-terminal autophosphorylation sites (Tyr1316 and Tyr1322) in receptor activation, we used (i) antipeptide antibodies against three different C-terminal sequences (1270-1281, 1294-1317, and 1309-1326) and (ii) an insulin receptor mutant (Y/F2) where Tyr1316 and Tyr1322 have been replaced by Phe. We show that the autophosphorylation-induced C-terminal conformational change is preserved in the Y/F2 receptor, indicating that this change is not induced by phosphorylation of the C-terminal sites but most likely by phosphorylation of the major sites in the kinase domain (Tyr1146, Tyr1150, and Tyr1151). Binding of antipeptide antibodies to the C-terminal domain modulated (activated or inhibited) both mutant and wild-type receptor-mediated phosphorylation of poly(Glu/Tyr). In contrast to the wild-type receptor, Y/F2 exhibited the same C-terminal configuration before and after insulin binding, evidencing that mutation of Tyr1316 and Tyr1322 introduced conformational changes in the C-terminus. Finally, the mutant receptor was 2-fold more active than the wild-type receptor for poly(Glu/Tyr) phosphorylation. In conclusion, the whole C-terminal region of the insulin receptor beta-subunit is likely to exert a regulatory influence on the receptor kinase activity. Perturbations of the C-terminal region, such as binding of antipeptides or mutation of Tyr1316 and Tyr1322, provoke alterations at the receptor kinase level, leading to activation or inhibition of the enzymic activity.

Adenosine Triphosphate↗

PubMed1993

Transmembrane signaling by an insulin receptor lacking a cytoplasmic beta-subunit domain.

To assess the function of the cytoplasmic domain of the insulin receptor (IR) beta subunit, we have studied a mutant IR truncated by 365 aa (HIR delta 978), thereby deleting > 90% of the cytoplasmic domain. HIR delta 978 receptors were processed normally to homodimers that were expressed at the cell surface where they bind insulin with normal affinity. Although these truncated IRs were inactive with respect to ligand-induced internalization and autophosphorylation, insulin stimulated endogenous substrate (pp185) phosphorylation significantly more in HIR delta 978 cells than in untransfected Rat1 cells. Importantly, despite absence of the beta-subunit cytoplasmic domain, fibroblasts expressing HIR delta 978 receptors displayed enhanced sensitivity to insulin for stimulation of glucose incorporation into glycogen, alpha-aminoisobutyric acid uptake, thymidine incorporation, and S6 kinase activity compared with parental fibroblasts. Insulin also induced the expression of the protooncogene c-fos and the early growth response gene Egr-1 in HIR delta 978 cells far greater than in parental Rat1 fibroblasts. Furthermore, an agonistic monoclonal antibody specific for the human IR stimulated insulin action in fibroblasts expressing wild-type human IR but had no effect on HIR delta 978 cells. In conclusion, the HIR delta 978 truncated IRs appear to confer enhanced insulin sensitivity by augmenting the signaling properties of the endogenous rodent IRs.

Aminoisobutyric Acids↗

PubMed1993

Structure of the gene encoding rat neutrophil chemo-attractant Gro.

A cloned rat gro gene encoding the neutrophil chemo-attractant Gro was isolated from a lambda Charon4A rat genomic library, and the nucleotide (nt) sequence of a 2500-bp fragment encompassing the coding region and 3'- and 5'-flanking regions was determined. The gene consisted of four exons separated by three introns. The transcription start point was determined by primer-extension analysis and found to be a G located 72 nt upstream from the start codon. The 5'-flanking region of the gene contained a 'TATA'-like structure and an NF-kappa B-binding sequence.

Amino Acid Sequence↗

PubMed1993

A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance.

We evaluated a 35-year-old diabetic male patient with type A insulin resistance, showing acanthosis nigricans. Insulin binding to the patient's Epstein-Barr-virus transformed lymphocytes was mildly reduced. The maximal insulin-stimulated autophosphorylation of the insulin receptor from the patient's transformed lymphocytes was decreased to 45% of that from the control subjects. On examination, the biological activities of insulin and insulin-like growth factor I in the patient's cultured fibroblasts, insulin sensitivity of amino isobutyric acid uptake and thymidine incorporation was decreased, but insulin-like growth factor I action was normal. The sequence analysis of amplified genomic DNA revealed that the patient was heterozygous for a mutation substituting Leu for Trp at codon 1193 in exon 20 of the insulin receptor gene. The patient's mother and sister were also heterozygous for a mutation in the insulin receptor gene that substituted Leu for Trp1193 in the beta subunit of the receptor. Therefore, the mutation causes insulin resistance in a dominant fashion. They were less hyperglycaemic and more hyperinsulinaemic than the proband after glucose loading. The mother had diabetes mellitus but did not show acanthosis nigricans, while the sister did not have diabetes and showed acanthosis nigricans. These results suggest that this mutation causes defective tyrosine kinase activity of the insulin receptor, which results in insulin resistance. Insulin action and phenotypic appearance may be mediated by different factors.

Adult↗

PubMed1993

Recombinant expression of rat and human Gro proteins in Escherichia coli.

A full-length rat gro cDNA containing the signal sequence was inserted to a plasmid/phage vector pTD-lacs which had the Escherichia coli alkaline phosphatase leader sequence down-stream of the lac promoter. After removal of the gro signal sequence by site-directed mutagenesis, the vector was introduced to E. coli JM109. The cells grown in the presence of isopropyl beta-D-thiogalactopyranoside were found to contain the recombinant mature rat Gro protein in the periplasmic space. The protein was released from the cells by osmotic shock, and could be purified to homogeneity from the periplasmic fluid by a single-step procedure using reverse phase high performance liquid chromatography. By similar procedures, recombinant human Gro alpha could be obtained. In each case, about 10 mg of purified cytokine were obtained from 1 litre of bacterial culture.

Animals↗

PubMed1993

Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery.

This study was designed to determine the age-related changes in the endothelium-dependent hyperpolarization to acetylcholine (ACh) and its contribution to relaxation in the isolated mesenteric artery from normotensive and hypertensive rats. Membrane potentials and contractions were recorded in arteries from male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) that were 5-6 wk old (young), 6-8 mo old (adult), and 20-26 mo old (aged). Endothelium-dependent hyperpolarizations produced by ACh, applied both at the resting state of the membrane and under conditions of depolarization with norepinephrine (10(-5) M), were markedly impaired in aged WKY rats, adult SHR, and aged SHR. Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were also impaired in aged WKY rats, adult SHR, and aged SHR even in the presence of indomethacin. Furthermore, in these rats, N omega-nitro-L-arginine, an inhibitor of nitric oxide formation, showed potent inhibitory effects on the relaxations, whereas the 20 mM high K+ solution that reduces hyperpolarization had less pronounced effects. Hyperpolarizations and relaxations to cromakalim (10(-5) M), a K(+)-channel opener, were on the whole preserved in aged rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced with aging as well as by hypertension, and this would, in part, account for the impaired relaxation to ACh in arteries of both aged rats and hypertensive rats.

Acetylcholine↗

PubMed1993

Voltage-dependent Ca2+ channels in resistance arteries from spontaneously hypertensive rats.

Alterations in voltage-dependent Ca2+ channels in the arterial smooth muscle cells of spontaneously hypertensive rats (SHR) were investigated using the whole-cell voltage clamp and compared with Wistar-Kyoto (WKY) rats. Single cells were freshly isolated from resistance mesenteric arteries from 4- to 5-week-old (young) and 16- to 18-week-old (adult) SHR. Elevated blood pressure was only evident in adult SHR, not in young SHR. In young rats, the Ca2+ channel current density (current amplitude normalized by cell capacitance) was significantly higher (P < .01) in SHR than in WKY rats at the command potential of -10 mV or higher (with 50 mmol/L Ba2+): The current density at 20 mV was -16.8 +/- 1.1 pA/pF in SHR (n = 38 cells) and -11.0 +/- 0.8 pA/pF in WKY rats (n = 30 cells). In adult rats, the difference in current densities disappeared: -15.9 +/- 1.3 pA/pF in SHR (n = 25 cells) and -15.6 +/- 1.5 pA/pF in WKY rats (n = 29 cells). The ratio of maximal amplitude of T-type current to that of L-type current was low in young SHR (0.10 +/- 0.01) compared with the other three groups (0.16 to 0.20). Neither the activation curve nor the steady-state inactivation curve of SHR was different from that of age-matched WKY rats. However, the activation curves in adult rats were shifted to a hyperpolarized direction compared with those of young rats in both strains. These results suggest that the increased activity of voltage-dependent L-type Ca2+ channels of resistance arteries in young SHR may be related to the development of hypertension. The changes observed in adult rats may be due to a secondary modification of the channel during maturation and the presence of hypertension.

Animals↗

PubMed1993

A truncated human insulin receptor missing the COOH-terminal 365 amino acid residues does not undergo insulin-mediated receptor migration or aggregation.

A previous study of tyrosine kinase-defective insulin receptors demonstrated that receptor autophosphorylation or tyrosine kinase activity was required for concentrating insulin receptors in coated pits, but not for their migration or aggregation on the cell surface. Furthermore, receptor migration and aggregation on the cell surface were not sufficient to cause internalization of the occupied receptors in coated pits. In the present study, biochemical and ultrastructural techniques were used to compare insulin receptor mobility and internalization in Rat 1 fibroblasts expressing wild-type human insulin receptors (HIRc) with those in cells expressing receptors truncated at residues 978 (HIR delta 978) or 1301 of the carboxyl-terminus (HIR delta CT). There were no significant differences in the mobility or internalization of insulin receptors on HIR delta CT cells compared to those of insulin receptors on HIRc cells. Ultrastructural analysis revealed that truncated insulin receptors on HIR delta 978 cells failed to migrate from their initial location on the microvilli, move to the plasma membrane, and aggregate in coated pits. Receptor-mediated insulin internalization in HIR delta 978 cells was markedly decreased due entirely to a decrease in ATP-dependent, coated pit-mediated internalization. ATP-independent endocytosis in non-coated pinocytotic invaginations was not affected by receptor truncations. These results provide evidence of the roles that regions of the beta-subunit play in the processing of occupied insulin receptors. 1) The carboxyl-terminus of the insulin receptor is not involved in the events leading to receptor internalization, i.e. migration, aggregation, and concentration in coated pits. 2) Internalization of insulin receptors by the ATP-independent noncoated invagination pathway is not regulated by residues in the insulin receptor beta-subunit distal to 978. 3) Sequences in the beta-subunit between 978-1300, but not the autophosphorylation and kinase domains, are involved in insulin-induced receptor migration and aggregation.

Amino Acid Sequence↗

PubMed1993

Gene structure of bovine adrenodoxin reductase.

The gene structure of bovine adrenodoxin reductase, a component of the mitochondrial steroid hydroxylating system in the adrenal cortex, was determined. When we screened a bovine genomic DNA library, using bovine adrenodoxin reductase cDNA as a probe, we isolated 10 genomic clones covering a continuous 30 kilobase (kb) region of bovine chromosomal DNA in which the adrenodoxin reductase gene spanned approximately 12 kb. The adrenodoxin reductase gene consisted of 12 exons and all the donor and acceptor sites of the exon/intron junction followed the GT/AG rule. The transcription initiation site was found to be 79 bases upstream of the translation initiation site by primer extension analysis and putative CAAT and GC boxes, but no typical TATA box, were present in the 5'-flanking region. The 5'-flanking region of this gene showed several features characteristic of promoters of house-keeping genes. The CCAGGG sequence present in the 5'-flanking region of genes for adrenodoxin and the steroid hydroxylating cytochromes P-450 in the adrenal cortex was present 13 bases upstream from the transcription initiation site. We analyzed the promoter activity of the 5'-upstream region of this gene, using as a reporter the chloramphenicol acetyltransferase gene. The region between position -757 to -376 was proved necessary for expression of this gene in mouse Y-1 tumor cells. Adrenocorticotropin did not enhance the expression of this bovine gene in the cells.

Amino Acid Sequence↗

PubMed1993

Direct expression of adrenodoxin reductase in Escherichia coli and the functional characterization.

A plasmid for direct expression in Escherichia coli of the mature form bovine adrenodoxin reductase was constructed from the full-size cDNA for the enzyme [Y. Sagara, Y. Takata, T. Miyata, T. Hara, and T. Horiuchi, J. Biochem. (Tokyo), 102, 1333 (1987)] and an expression vector pCWori+. The recombinant adrenodoxin reductase was purified from the transformed E. coli cell lysates using adrenodoxin-Sepharose affinity chromatography [T. Sugiyama and T. Yamano, FEBS Lett., 52, 145 (1975)] with a yield of 2.5 mg/l of culture. The purified recombinant enzyme showed a single band on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and migration was identical with that of the authentic enzyme purified from bovine adrenal cortex mitochondria. The recombinant enzyme had Ser at its amino-terminus and the sequence of the amino terminal 9 residues was identical with that of the authentic bovine enzyme. The absorption spectrum of the recombinant enzyme showed peaks at 270, 376, and 450 nm and shoulders at 425 and 475 nm. Flavin content of the recombinant enzyme was 0.8 mol FAD/mol. The apparent Km value for bovine adrenodoxin in NADPH-cytochrome c reductase activity using a reconstitution system was 16 nM, a value comparable with that of the authentic bovine enzyme (17 nM). The cholesterol side chain cleavage activity with a reconstitution system was about 75% of that obtained when the authentic enzyme was used.

Adrenal Cortex↗

PubMed1993

Possible involvement of ATP-sensitive K+ channels in the inhibition of rat central adrenergic neurotransmission under hypoxia.

By using rat brain cortical slices preloaded with [3H]norepinephrine, we examined whether ATP-sensitive K+ channels are involved in altered adrenergic neurotransmission during hypoxia. The tritium overflow evoked by transmural nerve stimulation (TNS) was significantly inhibited at 5 min of hypoxia and reached the maximum inhibition at 20 min. The inhibition of the TNS-evoked tritium overflow under a 20-min hypoxia was reversed by subsequent reoxygenation and was concentration-dependently antagonized by glibenclamide (0.1 and 1 microM). 86Rb+ efflux was increased after introduction of hypoxia and reached the peak value at about 20 min, which was concentration-dependently antagonized by glibenclamide (0.1-10 microM). Hypoxia decreased cortical ATP content. Linear correlations were mutually observed among the changes by hypoxia in the TNS-evoked tritium overflow, tissue ATP content and 86Rb+ efflux. The spontaneous tritium outflow was inhibited only after hypoxic periods of more than 16 min, the inhibition being reversed by reoxygenation and antagonized by 1 microM glibenclamide. These results suggest that the inhibition of rat central adrenergic neurotransmission during hypoxia may be associated with an activation of ATP-sensitive K+ channels.

Adenosine Triphosphate↗