The sodium-activated potassium channel Slack is modulated by hypercapnia and acidosis.

Slack (Slo 2.2), a member of the Slo potassium channel family, is activated by both voltage and cytosolic factors, such as Na(+) ([Na(+)](i)) and Cl(-) ([Cl(-)](i)). Since the Slo family is known to play a role in hypoxia, and since hypoxia/ischemia is associated with an increase in H(+) and CO(2) intracellularly, we hypothesized that the Slack channel may be affected by changes in intracellular concentrations of CO(2) and H(+).

Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression.

Affective disorders often occur in combination with disrupted sleep-wake cycles and abnormal fluctuations in hypothalamic neurotransmitters. Hypocretin (orexin) is a hypothalamic neuropeptide linked to narcolepsy, a sleep-related disorder characterized by profound disturbances in the normal sleeping pattern and variable degrees of depression. Wistar-Kyoto (WKY) rats exhibit depressive characteristics and patterns of sleep disruption similar to that observed in depressed human patients.

Expression of alpha-7 nAChRs on spinal cord-brainstem neurons controlling inspiratory drive to the diaphragm.

In the present study, we determined whether alpha-7 subunit containing nicotinic acetylcholine receptors (nAChRs) are expressed by neurons within the pre-Botzinger complex (pre-BotC), bulbospinal, and phrenic motor nuclei in the rat. alpha-7 Immunohistochemistry combined with cholera toxin B (CTB), a retrograde tracer was used to detect expression of alpha-7 nAChRs by phrenic motor and bulbospinal neurons. Neurokinin-1 receptor immunoreactivity was used as a marker for pre-BotC neurons.

Paraventricular vasopressin-containing neurons project to brain stem and spinal cord respiratory-related sites.

We studied in the rat projections of vasopressin-containing neurons of the paraventricular nucleus (PVN) to phrenic nuclei and to the pre-Botzinger complex (pre-BotC). In addition, we determined vasopressin receptor expression within the pre-BotC and the physiological effects of vasopressin on respiratory drive and arterial blood pressure when injected into the pre-BotC. Retrograde tracing with cholera toxin B subunit (CT-b) showed that a subpopulation of vasopressin-containing PVN neurons project to phrenic nuclei and the pre-BotC.

CO(2)-induced c-Fos expression in hypothalamic vasopressin containing neurons.

Following exposure of anesthetized and unanesthetized rats to hypercapnic stress, arginine vasopressin (AVP)-containing neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei were examined for expression of the c-fos gene encoded protein (c-Fos). In addition, we determined whether AVP-containing PVN neurons activated by hypercapnia project to phrenic nuclei. In adult control rats, only scant c-Fos-like immunoreactive neurons were observed within the hypothalamic nuclei.

Synergism between cocaine and atropine at the caudal ventrolateral medulla of cats.

We have previously reported that the anticholinergic properties of cocaine may be important in cocaine induced apneusis. We have studied the effects of the cholinergic muscarinic antagonist atropine (ATR) on cocaine induced apneusis at the caudal chemosensitive areas of the ventrolateral medulla oblongata (CVLM). Experiments were performed in urethane anesthetized and tracheotomized cats with the CVLM surgically exposed.

Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons.

Physiological evidence has indicated that central respiratory chemosensitivity may be ascribed to neurons located at the ventral medullary surface (VMS); however, in recent years, multiple sites have been proposed. Because c-Fos immunoreactivity is presumed to identify primary cells as well as second- and third-order cells that are activated by a particular stimulus, we hypothesized that activation of VMS cells using a known adequate respiratory stimulus, H(+), would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stimulation of rostral and caudal VMS respiratory chemosensitive sites in chloralose-urethane-anesthetized rats with acidic (pH 7.

Cardiorespiratory effects of cocaine and procaine at the ventral brainstem.

The caudal ventrolateral medulla (CVLM) is an area of the brainstem, in the vicinity of the hypoglossal nerve roots, where cholinergic and adrenergic neurons participate in respiratory and vasomotor control. Cardiorespiratory depression has been produced by topical application of cocaine to the CVLM. In the present studies, the effects of topical pretreatments of the CVLM with alpha-adrenergic blockers (prazosin 4.

Effects of cholinomimetics on cocaine-induced hypotension and apneusis at a ventral brainstem cardiorespiratory control site.

The current study was undertaken to evaluate the effects of cholinomimetic drugs on cocaine-induced central cardiorespiratory depression. Cats anesthetized by urethane (2.0 g/kg) were subjected to topical application at the caudal ventrolateral medullary surface (cVMS) of cocaine and two cholinomimetic pretreatment drugs.

Central cocaine neurotoxicity at brainstem cardiorespiratory control sites.

Cocaine hydrochloride was applied topically to the ventrolateral medullary surface (VMS) where chemosensitive respiratory and vasomotor control sites are colocalized. Cats (n = 16) were anesthetized with urethane (2.0 g/kg, 80 percent of dose titrated over 60 min).

Cholinergic-opioid interactions at brainstem respiratory chemosensitive areas in cats.

Central respiratory chemosensitivity has been ascribed to CO2-sensitive neurons located on the ventral brainstem surface. The effects of cholinergic mechanisms on CO2-sensitive neuronal activity recorded extracellularly at the brainstem respiratory chemosensitive area at the caudal ventral medullary surface (cVMS) were investigated in cats (n = 14) anesthetized with chloralose-urethane. The neurons increased their firing rate from 10.

Naloxone application to the ventrolateral medulla enhances the respiratory response to inspired carbon dioxide.

Previous studies have shown that systemic administration of the opiate antagonist naloxone potentiates the ventilatory response to inspired carbon dioxide. The present study was designed to localize the site of action of naloxone for increasing the respiratory chemosensitivity to inhaled carbon dioxide (CO2) in cats. Naloxone applied topically to the caudal chemosensitive area on the ventral medullary surface (VMS) during hypercapnic breathing produced a 75% greater increase in minute ventilation than hypercapnic breathing alone.

Age differences in responsiveness of brainstem chemosensitive neurons to extracellular pH changes.

The sensitivity of neurons in the caudal chemosensitive area on the ventrolateral surface of the medulla oblongata (VMS) to extracellular pH changes was examined in newborn and young developing kittens and compared to that of adult cats. The pH was varied by superfusion of the VMS with mock cerebrospinal fluid (CSF) of pH 7.4 (control), 7.

The role of hypoxia in organophosphorus nerve agent intoxication.

Effectiveness of the standard therapy for organophosphorus (OP) anticholinesterase poisoning has been questioned because of the relative resistance of the cholinesterase (ChE) enzymes to reactivation by oximes (Harris et al., 1968). Because tissue hypoxia may be a significant lethal component of OP nerve agent intoxication, oxygen therapy should be beneficial.

Vasopressor responses and hypoxemia with acutely increased intracranial pressure.

We studied anesthetized dogs subjected to graded increases in intracranial pressure (ICP) to assess the role of the systemic vasopressor (Cushing) response in the arterial hypoxemia associated with increased ICP. The arterial PO2 decrement was significantly greater with rapidly increased ICP compared to slowly increased ICP (P less than 0.01).

Amelioration of hypoxemia by neuromuscular blockade following brain injury.

Brain injury has been commonly associated with respiratory failure and uncontrolled skeletal muscle activity. In the present study, neuromuscular (NM) blockade induced by injection of succinylcholine hydrochloride was used to block uncontrolled muscle contractions in dogs with brain injury caused by rapid elevation of intracranial pressure (ICP). Decerebrate posturing, a decrease in value (mean +/- SEM) of arterial oxygen tension (Pa02) of 26 +/- 1 torr, and an increase in arterial carbon dioxide tension (PaCO2) of 11 +/- 1 torr occurred in the dogs, which were supported by mechanical ventilation.

Neurophysiological studies on superficial medullary chemosensitive area for respiration.

In cats anesthetized with chloralose-urethane (40 mg/kg chloralose; 200 mg/kg urethane) pH sensitivity of neurons in the caudal chemosensitive area on the ventrolateral surface of the medulla oblongata was examined while monitoring phrenic nerve activity simultaneously. pH was varied by superfusion of the ventral medullary surface with mock cerebrospinal fluid (CSF) of different pH (pH 7.4 control, 7.

Morphological observations on superficial medullary CO2--chemosensitive areas.

Physiological investigations have indicated that the ventrolateral surface of the medulla oblongata is involved in the chemical drive to respiration. In this investigation, light and electron microscopic investigations of the 3 chemosensitive regions reveal the following. (1) Evaginations of the ventral surface abut the overlying pia mater thereby delimiting discrete compartments; invaginations of the surface delimit wide cisternae lined with basement membrane.

Analysis of the sexual dimorphism in the basioccipital portion of the dog's skull.

Sexual differences in the basioccipital portion of the skull of dogs have been described and an index is presented which reliably predicts the sex of the skull. 92 dolichocephalic skull (44 male, 48 female) from mongrel dogs were used. In the basioccipital region of the male skulls, a triangular area, which extends from the basion to a line joining the medialmost points of the two jugular foramina, appears narrow and elevated.

Sexual dimorphism in the basilar part of the occipital bone of the dog (Canis familiaris).

Sexual dimorphism in the surface markings of the basilar part of the occipital bone of 34 male and 46 female dog's skulls were studied with the following results: 1 of the 34 male skulls showed a female type surface marking, 4 of the 46 female skulls showed surface markings of the opposite sex, while 2 of the male and 3 of the female skulls could not be classified as belonging to either type, so that 10 out of the 80 skulls could not be identified correctly, indicating that 87.5% of the skulls could be identified positively. Considering that there are hardly any sexual differences in the other surface markings or in the dentition of the dog's skull, these findings may be of some help in sexing the skull of the dog.