Arrest Of Respiration Research Articles

OXPHOS capacity is diminished and the phosphorylation system inhibited during diapause in an extremophile, embryos of Artemia franciscana.

Diapause exhibited by embryos of Artemia franciscana is accompanied by severe arrest of respiration. A large fraction of this depression is attributable to downregulation of trehalose catabolism that ultimately restricts fuel to mitochondria. This study now extends knowledge on the mechanism by revealing metabolic depression is heightened by inhibitions within mitochondria. Compared with that in embryo lysates during post-diapause, oxidative phosphorylation (OXPHOS) capacity P is depressed during diapause when either NADH-linked substrates (pyruvate and malate) for electron transfer (electron transfer capacity, E) through respiratory Complex I or the Complex II substrate succinate are used. When pyruvate, malate and succinate were combined, respiratory inhibition by the phosphorylation system in diapause lysates was discovered as judged by P/E flux control ratios (two-way ANOVA; F1,24=38.78; P<0.0001). Inhibition was eliminated as the diapause extract was diluted (significant interaction term; F2,24=9.866; P=0.0007), consistent with the presence of a diffusible inhibitor. One candidate is long-chain acyl-CoA esters known to inhibit the adenine nucleotide translocator. Addition of oleoyl-CoA to post-diapause lysates markedly decreased the P/E ratio to 0.40±0.07 (mean±s.d.; P=0.002) compared with 0.79±0.11 without oleoyl-CoA. Oleoyl-CoA inhibits the phosphorylation system and may be responsible for the depressed P/E in lysates from diapause embryos. With isolated mitochondria, depression of P/E by oleoyl-CoA was fully reversed by addition of l-carnitine (control versus recovery with l-carnitine, P=0.338), which facilitates oleoyl-CoA transport into the matrix and elimination by β-oxidation. In conclusion, severe metabolic arrest during diapause promoted by restricting glycolytic carbon to mitochondria is reinforced by depression of OXPHOS capacity and the phosphorylation system.

Pulsatile Features of Major Arteries in Rats during Hypotension Caused by Acute Blood Loss.

The study examined the modes of pulsations of the femoral and carotid arteries of rats in situ (n=14) during acute blood loss, which sequentially caused a deep BP drop, cardiac and respiration arrest, and termination of ECG signals. When BP dropped to 19 (13; 26) mm Hg, the mechanosensitivity of passively pulsing arteries determined by the ratio of the swing range of electroimpedance oscillations of arterial segment to pulse pressure increased by 3.2 (2 ; 4) times (p<0.05). During the decrease of BP to the threshold value of 13 (8; 15) mm Hg, the arterial pulsing mode changed from passive to intermediate and then to the active one characterized by constriction of arterial segment in response to systolic elevation of BP. After cardiac arrest and BP drop almost to zero, the arterial pulsing switched to autonomic rhythmical vasomotions with the rate, which was greater than the frequency of still sustained QRS pulses of ECG. The observed phenomena are explained by transarterial hypotensive transition hypothesis, which argues that peculiarities of pulsations and vasomotions of major arteries during deep BP drop are typical of arterioles under normal or diminished BP. The study refined the hypothesis of "peripheral heart" and its role in hypo- and hypertension.

Complex Visceral Coupling During Central Sleep Apnea in Cats.

Central sleep apnea is a sudden arrest of breathing during sleep caused by the central commands to the thoracoabdominal muscles. It is a widespread phenomenon in both healthy and diseased people, as well as in some animals. However, there is an ongoing debate whether it can be considered as a pathological deviation of the respiratory function or an adaptive mechanism of an unclear function. We performed chronic recordings from six behaving cats over multiple sleep/wake cycles, which included electroencephalogram, ECG, eye movements, air flow, and thoracic respiratory muscle movements, and in four cats combined that with the registration of myoelectric activity of the stomach and the duodenum. In these experiments, we observed frequent central cessations of breathing (for 5–13 s) during sleep. Each of the sleep apnea episodes was accompanied by a stereotypical complex of somatic and visceral effects. The heart rate increased 3–5 s before the respiration arrest and strongly decreased during the absence of respiration. The myoelectric activity of the stomach and the duodenum also often demonstrated a strong suppression during the apnea episodes. The general composition of the visceral effects was stable during all periods of observation (up to 3 years in one cat). We hypothesize that the stereotypic coupling of activities in various visceral systems during episodes of central sleep apnea most likely reflects a complex adaptive behavior rather than an isolated respiratory pathology and discuss the probable function of this phenomenon.

Enzymatic assays for probing mitochondrial apoptosis.

Isolated mitochondria are an invaluable analytical tool to probe mitochondrial function and evaluate apoptosis induction via the so-called mitochondrial pathway. Irrespective of their tissue origin (e.g., heart, liver, muscle, brain), these organelles participate actively to cell and life decision by producing energy for cell metabolism, but also by undergoing a lethal and irreversible mitochondrial membrane permeabilization (MMP) in stress and pathological conditions. MMP consequences consist, at least in part, in loss of mitochondrial transmembrane potential (ΔΨm), matrix swelling, arrest of respiration and ATP production, and cytochrome c release from the intermembrane space to the cytosol. These parameters can be evaluated in vitro via several miniaturized assays, which have tremendous applications in the field of pharmacology, toxicology, diagnosis, as well as drug discovery.

RESUSCITATION OF VITAL ACTIVITY AFTER COLD ARREST OF RESPIRATION BY PHYSIOLOGICAL METHODS WITHOUT REWARMING THE BODY

The arrest of respiration during deep hypothermia means death, though at a low temperature the heart may rhythmically contract for 30–40 minutes more. The attempts of rewarming only shorten the time before the heart arrest. “The aim of the study” the attempts to develop the methods of stimulating the respiration and heart without rewarming the body. Calcium ions (Ca2+) are believed to accumulate in the nervous cells in cold. An excess of these ions inhibits the metabolism. Moreover it stimulates the cell proteases, which destroy the cell membranes. “Materials and methods” The work was carried out on wite rats 250-320 g in weight. We introduced disodium salt of ethylenediaminetetraacetic acid (EDTA) into the animals. The second method of blocking the mechanisms of the cold death was artificial respiration. “Results”EDTA reacts with calcium ions, decreases their quantity in the blood, and, consequently, in a complex manner in the cell protoplasm. Artificial respiration not only increases the flow of oxygen into an organism but also decreases the lowest temperature threshold of the cold death of an organism. “Conclusions” A decrease in the surviving threshold by 1.5-1.8oC is very important from the point of view of reanimation of an organism since to preserve life in the critical period of reanimation each 0.5oC are important. Prolongation of minimal frequency of heart contractions and maintaining a minimal arterial blood pressure in an overcooled organism given the body temperature of 11-12.5oC is a special problem of great interest associated with many physiological and biological parameters.

Resuscitation of vital activity after cold arrest of respiration by physiological methods without rewarming the body

The arrest of respiration during deep hypothermia means death, though at a low temperature the heart may rhythmically contract for 30-40 minutes more. The attempts of rewarming only shorten the time before the heart arrest. Calcium ions (Ca2+) are believed to accumulate in the nervous cells in cold. An excess of these ions inhibits the metabolism. Moreover it stimulates the cell proteases, which destroy the cell membranes. The aim of the study was to make the the attempts to develop the methods of stimulating the respiration and heart without rewarming the body. The work was carried out on wite rats 250-320g in weight. We introduced disodium salt of ethylenediaminetetraacetic acid into the animals. The second method of blocking the mechanisms of the cold death was artificial respiration. Ethylenediaminetetraacetic acid reacts with calcium ions, decreases their quantity in the blood, and, consequently, in a complex manner in the cell protoplasm. Artificial respiration not only increases the flow of oxygen into an organism but also decreases the lowest temperature threshold of the cold death of an organism. A decrease in the surviving threshold by 1.5-1.8 degrees C is very important from the point of view of reanimation of an organism since to preserve life in the critical period of reanimation each 0.5 degrees C are important. Prolongation of minimal frequency of heart contractions and maintaining a minimal arterial blood pressure in an overcooled organism given the body temperature of 11-12.5 degrees C is a special problem of great interest associated with many physiological and biological parameters.

An Unusual Suicide

Asphyxia by suffocating gases, that is, methane or carbon dioxide, is characterized by the displacement of oxygen from inspired air. Thus, the cells are unable to receive oxygen and, as a consequence, are affected by acute hypoxemic hypoxia. The brain suffers because of the hypoxemic state, the subject become unconscious, and then, respiration arrest occurs, followed by cardiac arrest. This is the physiopathologic mechanism leading to death.We report a case of a 35-year-old man found dead at home with his mouth containing a tube linked to the domestic methane gas system originating from the wall, sealed with packing tape.

Respiration Restitution in Rats Following Its Termination in Immersion Hypothermia

Rats were cooled in water until attaining profound hypothermia and respiratory arrest. After removal from water, 0.5% solution of Na2EDTA was administered intravenously. This led to a drop of blood [Ca2+] by 20-30% from the baseline and promoted recovery of respiration following its arrest lasting 10.3±1.4 min. By the 30th minute of Na2EDTA administration, respiration rate increased to 32.3±5.2 cycles per minute and respiration amplitude reached 68±4% of the baseline level. This effect was observed without special warming of the rats. It was concluded that the period during which the organism maintains viability in respiration arrest and disturbances in respiratory center are still reversible is prolonged under conditions of profound hypothermia.

Sexual behavior and locomotion induced by sexual cues in male rats following lesion of Lobules VIa and VII of the cerebellar vermis

The cerebellum is an important contributor to the neural basis of sexual behavior, but the specific cerebellar regions underlying different aspects of reproduction are still unknown. Here, we used experimental lesions of Lobules VIa and VII of the vermis to investigate their specific role, both in locomotion stimulated by sexual cues and the execution of sexual behavior. Sexually experienced male rats and receptive females were used, and experimental males received an electrolytic lesion of either lobule. Before and after the lesion, males were tested for sexual behavior, and for locomotion on a horizontal or ascending bar to reach an estrous female. The lesion of Lobule VIa produced impairments in intromission-related behaviors during copulation, and produced slippery footsteps that increased the time to cross the bars with a stronger effect on the ascending bar. The lesion of Lobule VII produced a dramatic arrest of respiration that precluded further behavioral tests. These results suggested that Lobule VIa is involved in the integration of sensory inputs coming from in-copula penile stimulation, implying the existence of a penis-cerebellum neural pathway for a proprioception-like process involved in the proper spatial orientation of the erected penis. Walking on bars showed an alteration of the stepping cycle that suggests the role of Lobule VIa in the fine tuning of locomotion spinal reflexes. The lesion of Lobule VII suggested its role in the physiology of respiration, a topic that deserves further research.

Assessment of vasomotor oscillations with Fourier analysis of biological tissue impedance

Fourier analysis revealed a number of periodicities in small variations of bioimpedance of human finger including the major spectrum peaks at the frequencies of heart beats, respiration, and Mayer wave (0.1 Hz). These periodic variations of bioimpedance were detected under the normal conditions and during blood flow arrest in the hand by a pneumatic cuff placed on the arm. They are explained by periodic variations in systemic blood pressure and by oscillations of regional vascular tone resulted from neural vasomotor control. During normal blood flow, the greatest variations in bioimpedance were observed at the heart rate, and their amplitude surpassed by an order of magnitude the amplitudes of respiratory oscillations and Mayer wave. In contrast, during blood arrest, the largest amplitude of rhythmical changes of the impedance characterized the oscillations at respiration rate, while the amplitude of oscillations at the heart rate was the smallest. During normal respiration and circulation, two side cardiac peaks were revealed in bioimpedance amplitude spectrum which disappeared during respiration arrest and thought to reflect the amplitude respiratory modulation of the cardiac output via sympathetic influences. During normal breathing, the second and the third harmonics of the cardiac spectrum peak were split reflecting frequency respiratory modulation of the heart rate by parasympathetic influences. The results favour applicability of Fourier analysis of bioimpedance variations in assessment of regional neural influences and neurogenic modulation of cardiac activity.

Transient Hyperoxic Reoxygenation Reduces Cytochrome c Oxidase Activity by Increasing Superoxide Dismutase and Nitric Oxide

Oxygen therapies have been shown to be cytoprotective in a dose-dependent fashion. Previously, we have characterized the protective effects of moderate hyperoxia on cell viability of ischemic human cardiomyocytes and their mitochondrial membrane potential by transient addition of oxygenated perfluorocarbons to the cell medium. Now, we report that the activity and expression of cytochrome c oxidase (COX) after prolonged ischemia depend on the amount of oxygen delivered during reoxygenation. Transient hyperoxia during reoxygenation results in a decrease of COX activity by 62 +/- 15% and COX expression by 67 +/- 5%, when hyperoxic tensions of approximately = 300 mm Hg are reached in the cell medium. This decrease in COX expression is prevented by the inhibition of inducible nitric-oxide synthase (iNOS). Immunoblot analysis of ischemic human cardiomyocytes revealed that hyperoxic reoxygenation causes a 2-fold increase of iNOS, leading to a rise in nitric oxide production by 140 +/- 45%. Hyperoxic reoxygenation is further responsible for a 2-fold activation of hydrogen peroxide production and an increase in cytosolic superoxide dismutase expression by 35 +/- 10%. NADPH availability has no effect on the hyperoxia-induced decrease of superoxide. Overall, these results indicate that transient hyperoxic reoxygenation in optimal concentrations increases the level of nitric oxide by activation of iNOS and superoxide dismutase, thereby inducing respiration arrest in mitochondria of ischemic cardiomyocytes.

Comparative-physiological study of leukocyte participation in initiation of lipid peroxidation during nitrite intoxication in rats and muskrats

The study is carried out on Wistar white rats non-adapted to oxygen deficit and on semiaquatic rodents muskrats adapted to periodic arrest of respiration during diving under conditions of Nembutal narcosis. It has been revealed that 1 h after a subcutaneous injection of sodium nitrite (3 mg/100 g body mass), intensification of lipid peroxidation (LPO) in the muskrat brain is absent, the activity of the antioxidant enzyme catalase increasing 16 times (p < 0/01) as compared with control injected with equivalent saline volume. In heart and liver, a statistically significant decrease of the content of LPO products active in the test with 2-thionarbituric acid; in the femoral muscle tissue, the LPO intensity does not change. In rats, unlike muskrats, after injection of sodium nitrite, an increase of LPO is recorded in brain, while a decrease of the LPO product content in the femoral muscle; in liver the LPO intensity did not change. In muskrats, the sodium nitrite administration leads to a decrease of the leukocyte spontaneous mobility, of lymphocyte cytokine-producing activity, and ofneutrophil bactericidal activity (by the content of cationic proteins in neutrophilic phagocytes), whereas in rats the leukocyte mobility does not change, only the blood neutrophil bactericidal activity decreases. The ability of neutrophils to produce the superoxide anion during the nitrite intoxication does not change both in rats and in muskrats. The obtained data allow concluding that under conditions of Nembutal narcosis the leukocyte functional activity on the background of nitrite intoxication is suppressed to the greater degree in the muskrats genotypically adapted to oxygen deficit than in immunocompetent cell of the rodents not adapted to hypoxia.

Regulatory peptides protect brain neurons from hypoxia in vivo

Short peptides that have been characterized in previous studies performed in the St. Petersburg Institute of Bioregulation and Gerontology of the Northeastern Division of the Russian Academy of Medical Sciences [1‐3] protect neurons from oxidative stress [4]; however, under in vitro conditions, the peptide action has been observed at high (millimolar) concentrations. The anti-oxidant activity of these peptides is not high; therefore, their biological effect could be mediated by a natural system of antioxidant defense [5]. If this is the case, the peptide protective effect could be observed at almost physiological concentrations under the in vivo conditions. This was aimed at verifying this assumption. The protective effect of short regulatory peptides (vilon, epitalon, pinealon, and vesugen) was studied under the conditions of oxidative stress caused in animals by hypobaric hypoxia. Male Wistar rats weighing 185‐200 g were used in our experiments. Oxidative stress was induced under the conditions of hypobaric hypoxia in an altitude chamber with adjustable airflow, which prevented hypercapnia [6]. By means of a vacuum pump, the pressure in the altitude chamber was reduced to 0.125 atm for 1 min. Under these conditions, the animals were kept until respiration arrest; after this, the animals were returned to the normal-pressure conditions by supplying air into the chamber for 1 min. The following parameters were recorded: the time (s) until the respiration arrest “at the height”; the time (s) of posture recovery, i.e., the period from respiration arrest to the moment when the experimental animal assumed normal posture after “descending from the height” and respiration recovery under normobaric conditions; and the restitution time (s), the total duration of the recovery of physiological activity after hypoxia. To determine the protective effect of the peptides studied, the death rate and coefficient of restitution (the ratio of the restitution time to the time before respiration arrest in the altitude chamber) were estimated. The results obtained were processed statistically using the Mann‐Whitney and Kruskal‐Wallis tests; the differences were assumed to be significant at p < 0.05. The peptides vilon (Lys-Glu), vesugen (Lys-GluAsp), pinealon (Glu-Asp-Arg), and epitalon (Ala-GluAsp-Arg) were injected daily at a dose of 10 µ g/kg body weight intraperitoneously for five days before hypoxia. The rats of the control group were injected with saline according to the same scheme. Each group contained 10 animals.

Changes in Hemodynamics and Respiration in Rats with Different Resistance to Acute Hypoxia

Effects of acute hypoxia on hemodynamics and respiration were studied in acute experiments on narcotized rats. The animals were divided into groups characterized by high, low-, and medium- resistance to hypoxia by the time of respiration arrest during inhalation of gas mixture containing 3% O2. Hemodynamic parameters of highly resistant animals were higher than in low-resistant rats throughout the entire hypoxic period. The development of a rare (with prolonged inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive reaction, which allows them longer tolerate hypoxia compared to low-resistant animals.

Activity of neurons in ventrolateral respiratory groups during swallowing in decerebrate rats

To elucidate the neuronal basis of the coordination between swallowing and respiration, we examined the swallowing-related activity of respiratory neurons in the ventrolateral respiratory groups of the medulla oblongata of decerebrate, paralyzed and artificially ventilated rats ( n=14). Extracellular recording was made during fictive swallowing evoked by the electrical stimulation of the superior laryngeal nerve from a total of 141 neurons with respiratory rhythm (99 expiratory and 42 inspiratory neurons). The burst of discharge by the hypoglossal nerve was used to monitor the pharyngeal phase of swallowing. The decrementing-expiratory (E-DEC) neurons ( n=62) were activated during ( n=46) or after ( n=10) the hypoglossal bursts, or showed no swallowing-related activity ( n=6). All of the augmenting-expiratory (E-AUG) neurons ( n=37) were silent during the hypoglossal bursts but were activated after each swallow. Inspiratory neurons showed either no swallowing-related bursts ( n=27), or were activated after the hypoglossal bursts ( n=15). Activation of the majority of E-DEC neurons may be related to the arrest of respiration during swallowing, and the post-swallow activation of E-AUG neurons may correspond to the expiratory phase that follows swallowing. We suggest that these behaviors of expiratory neurons are essential in the phase resetting of the respiratory cycle in association with the swallowing.

Vampires, Pasteur and reactive oxygen species: Is the switch from aerobic to anaerobic metabolism a preventive antioxidant defence in blood-feeding parasites?

Several species of parasites show a reduction of their respiratory activity along their developmental cycles after they start to feed on vertebrate blood, relying on anaerobic degradation of carbohydrates to achieve their energy requirements. Usually, these parasites choose not to breathe despite of living in an environment of high oxygen availability such as vertebrate blood. Absence of the ‘Pasteur effect’ in most of these parasites has been well documented. Interestingly, together with the switch from aerobic to anaerobic metabolism in these parasites, there is clear evidence pointing to an increase in their antioxidant defences. As the respiratory chain in mitochondria is a major site of production of reactive oxygen species (ROS), we propose here that the arrest of respiration constitutes an adaptation to avoid the toxic effects of ROS. This situation would be especially critical for blood-feeding parasites because ROS produced in mitochondria would interact with pro-oxidant products of blood digestion, such as haem and/or iron, and increase the oxidative damage to the parasite’s cells.

Paradoxical Cardiac Rhythm in Rat Pups as a Possible Analog of the Sick Sinus Syndrome

Experiments with simultaneous recordings of ECG, electrogram of myocardial fibers of the right ventricle and neurogram of the right branch of vagus or sympathetic nerves were carried out on 3–18-day old rat pups. The electric activity recordings were performed under both in vivo and in situ conditions at unilateral or bilateral pneumothorax. It is established that the change in the cholinergic system activation level produced prior to pneumothorax decelerates the rhythm of cardiac contractions (CC) and induces periods of more frequent CC. After pneumothorax, this syndrome becomes more pronounced. The periods of alternation of the slow and fast rhythms may last for up to 1–2 min. The development of the pathological process leads to development of the sino-auricular and atrio-ventricular blocks. There appears a pattern of CC changes and complexes of the ventricular electric potentials that occur in decasecond and then in minute rhythms and are separated by periods of total asystole or preserved potentials of atrial excitation. When the electrograms of myocardium were recorded in rat pups under conditions of bilateral pneumothorax without any pharmacological intervention, it was possible to see a distortion of the sinus rhythm of CC developing for 2–2.5 h after respiration arrest and similar to the above-described distortion. The appearance and development of the phenomenon of the atypical cardiac rhythm is not directly related to the firing patterns of vagus and sympathetic nerves. At the same time, a correlation is clearly seen between the amplitude–frequency modulation of CC and discharges of vagus. A contraction of groups of respiratory muscles lasts for up to 30 min after pneumothorax, with occasional discharges seen in neurogram even after the complete immobilization of the animal. The development of the pathological process reveals a certain similarity with the phenomenon described in literature as the sinus node syndrome (tachy–bradycardia syndrome, TBS). Based on analysis of the cardiac rhythm transformation, it is suggested that the clinical TBS is a consequence of recapitulation, i.e., a successive release of ancient rhythms of excitation due to an impair of regulatory mechanisms.

中耳真珠腫による脳膿よう例 脳外科的処置の時期をめぐって

A 46-year-old man, with a history of right otitis media since childhood, complained of right otalgia and aural discharge for a month. The patient was admitted immediately because of severe headache and mastoid destruction seen on X-ray films. On admission, he showed signs of meningeal irritation and an intracranial complication was suspected. Intensive chemotherapy was begun. CT scan was done on the next day and revealed massive destruction of the right mastoid. Emergency mastoidectomy was performed, and a cholesteatoma was found in the antrum and the mastoid. Headache was improved postoperatively, but a relatively well encapsulated abscess of the right temporal lobe was found by postoperative MRI. Following chemotherapy, sudden arrest of respiration occurred on the 14th postoperative day, and emergency craniotomy was done, but the patient died 3 days postoperatively.It has been reported by many authors that with the advance of diagnosis by imaging and therapeutic methods, the mortality of otogenic intracranial complications has been greatly reduced. Yet the mortality due to otogenic intracranial abscess has not been lowered enough. There are two therapeutic approaches: one is otologic surgery first, followed by neurosurgical treatment ; and the other is intracranial surgery first, followed by otologic treatment, waiting for the improvement of the general condition. In the present case, we treated the patient by the first method unsuccessfully. We discuss, with a review of the literature, the degree to which conservative treatment is possible after otologic surgery.

Terminal anoxic depolarization proceeds more slowly in the olfactory bulb than in the cerebral cortex of rats

The time course of terminal anoxic depolarization and of the concomitant [K +] e increase was compared in the cerebral cortex and olfactory bulb of rats anesthetized with pentobarbital. Respiration arrest elicited by (+)-tubocurarine induced a negative slow potential shift which reached 50% of maximum after 90 s in the cortex and after 180 s in the olfactory bulb ( n = 10). Bulbar [K +] e increased slowly to 16 mmol/l, then more rapidly to 40–60 mmol/l and reached 90 mmol/l after 10 min asphyxia ( n = 10). While the resting and maximal [K +] e levels were the same in the cortex and olfactory bulb, the fast [K +] e rise started in the olfactory bulb at a higher level (16 mmol/l) and proceeded at a slower rate (doubling time 14 s) than in the cortex, where the same values were 11 mmol/l and 5 s, respectively. It is argued that the olfactory bulb resistance to asphyxia is due to a powerful GABAergic inhibition which counteracts the autoregenerative ionic shift and accounts for the absence of spreading depression in this structure.

Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon.

The parB region of plasmid R1 encodes two genes, hok and sok, which are required for the plasmid-stabilizing activity exerted by parB. The hok gene encodes a potent cell-killing factor, and it is regulated by the sok gene product such that cells losing a parB-carrying plasmid during cell division are rapidly killed. Coinciding with death of the host cell, a characteristic change in morphology is observed. Here we show that the killing factor encoded by the hok gene is a membrane-associated polypeptide of 52 amino acids. A gene located in the Escherichia coli relB operon, designated relF, is shown to be homologous to the hok gene. The relF gene codes for a polypeptide of 51 amino acids, which is 40% homologous to the hok gene product. Induced overexpression of the hok and relF gene products results in the same phenomena: loss of cell membrane potential, arrest of respiration, death of the host cell and change in cell morphology. The parB region and the relB genes were cloned into unstably inherited oriC minichromosomes. Whereas the parB region also conferred a high degree of genetic stability to an oriC minichromosome, the relB operon (with relF) did not; therefore the latter does not appear to 'stabilize' its replicon (the chromosome). The function of the relF gene is not known.