The present study was conducted to establish whether chronic salt loading alone, or in combinatio... more The present study was conducted to establish whether chronic salt loading alone, or in combination with the mineralocorticoid deoxycorticosterone acetate (DOCA), alters the content of sodium (Na+), potassium (K+) and calcium (Ca2+) in the brain. Male Sprague Dawley rats were implanted with a silicone pellet containing 0 (n=6) or 100 (n=6) mg DOCA and given 0.9% saline to drink ad libitum. The control group received 0mg DOCA and water ad libitum (n=6). After 21 days of treatment rats were anesthetized and brains were excised. The brainstem was removed and the remainder of the brain was bisected midsagitally. The right half of the brain was weighed intact and the left half was dissected into hypothalamus and cortex. Samples were analyzed for Na+/K+/Ca2+ content (ppm/gram) by inductively coupled argon plasma optical emission spectrometry. Compared to the control group, saline loading alone had no effect on Na+/K+/Ca2+ in any brain region. However, DOCA‐salt treatment increased Na+ (p < 0.05), and tended to decrease K+ content (p >; 0.05), in the hypothalamus but had no effect in the cortex or brainstem. DOCA‐salt treatment also increased hypothalamic (p < 0.05), but not cortical or brainstem, Ca2+ content. We conclude that regulation of hypothalamic Na+/K+/Ca2+ content is unique compared to the cortex and brainstem. HL64176–05
Mitochondrial dysfunction and induction of the mitochondrial permeability transition (MPT) are ca... more Mitochondrial dysfunction and induction of the mitochondrial permeability transition (MPT) are candidate intermediate steps in both necrotic and apoptotic cell death pathways (Dubinsky and Levi, 1998; Hirsch et al., 1998; Schinder et al., 1996). In its classic definition (referred to here as the high-conductance MPT), the MPT is a nonselective, multiconductance pore in the inner mitochondrial membrane whose activation causes mitochondrial swelling and dysfunction (Nieminen et al., 1996; Schinder et al., 1996; Zoratti and Szabo, 1995). In liver and heart mitochondria, accumulation of excess matrix calcium combined with phosphate or with an oxidative event leads to opening of the high conductance MPT pore (Zoratti and Szabo, 1995). Induction of the MPT is modulated by mitochondrial membrane potential , matrix free fatty acids, redox status of mitochondrial protein thiols, and surface potential generated by the largely anionic phospholipids of the inner mitochondrial membrane (Zoratti and Szabo, 1995). Pharmacological inhibition of the MPT can be accomplished with the immunosuppressant cyclosporin and some of its analogs, adenine nucleotides, and the adenine nucleotide transporter inhibitor bongkrekic acid (Zoratti and Szabo, 1995). Mitochondrial swelling as measured by changes in absorbance has typically been studied in mitochondria after loading. High loads alone, or lower plus phosphate, uncoupler, or pro-oxidants, initiates transition, a process thought to propagate through the mitochondrial population (Bernardi, 1992; Broekemeier et al., 1989). When ruthenium red (RR) is added after to prevent its loss through reverse operation of the uniporter, application of
We have found that the incidence of functionally connected neuron‐myotube pairs in chick ciliary‐... more We have found that the incidence of functionally connected neuron‐myotube pairs in chick ciliary‐myotube cultures increases from 58% to more than 90% when the cells are treated for several hours with 8‐bromo‐cyclic adenosine monophosphate (8‐br‐cAMP) or with agents known to increase intracellular cAMP. The increase in connectivity was not accompanied by a change in neuron survival, or in the length of neurite‐myotube contact. Moreover, there was no change in the shape of the presynaptic action potential, in mean end plate potential (epp) amplitude or in the sensitivity of postsynaptic acetylcholine receptors (AChRs). One interpretation of these results is that a cAMP‐dependent phosphorylation acts as a trigger to activate a previously “silent” synapse.
The present study was conducted to establish whether chronic salt loading alone, or in combinatio... more The present study was conducted to establish whether chronic salt loading alone, or in combination with the mineralocorticoid deoxycorticosterone acetate (DOCA), alters the content of sodium (Na+), potassium (K+) and calcium (Ca2+) in the brain. Male Sprague Dawley rats were implanted with a silicone pellet containing 0 (n=6) or 100 (n=6) mg DOCA and given 0.9% saline to drink ad libitum. The control group received 0mg DOCA and water ad libitum (n=6). After 21 days of treatment rats were anesthetized and brains were excised. The brainstem was removed and the remainder of the brain was bisected midsagitally. The right half of the brain was weighed intact and the left half was dissected into hypothalamus and cortex. Samples were analyzed for Na+/K+/Ca2+ content (ppm/gram) by inductively coupled argon plasma optical emission spectrometry. Compared to the control group, saline loading alone had no effect on Na+/K+/Ca2+ in any brain region. However, DOCA‐salt treatment increased Na+ (p < 0.05), and tended to decrease K+ content (p >; 0.05), in the hypothalamus but had no effect in the cortex or brainstem. DOCA‐salt treatment also increased hypothalamic (p < 0.05), but not cortical or brainstem, Ca2+ content. We conclude that regulation of hypothalamic Na+/K+/Ca2+ content is unique compared to the cortex and brainstem. HL64176–05
Mitochondrial dysfunction and induction of the mitochondrial permeability transition (MPT) are ca... more Mitochondrial dysfunction and induction of the mitochondrial permeability transition (MPT) are candidate intermediate steps in both necrotic and apoptotic cell death pathways (Dubinsky and Levi, 1998; Hirsch et al., 1998; Schinder et al., 1996). In its classic definition (referred to here as the high-conductance MPT), the MPT is a nonselective, multiconductance pore in the inner mitochondrial membrane whose activation causes mitochondrial swelling and dysfunction (Nieminen et al., 1996; Schinder et al., 1996; Zoratti and Szabo, 1995). In liver and heart mitochondria, accumulation of excess matrix calcium combined with phosphate or with an oxidative event leads to opening of the high conductance MPT pore (Zoratti and Szabo, 1995). Induction of the MPT is modulated by mitochondrial membrane potential , matrix free fatty acids, redox status of mitochondrial protein thiols, and surface potential generated by the largely anionic phospholipids of the inner mitochondrial membrane (Zoratti and Szabo, 1995). Pharmacological inhibition of the MPT can be accomplished with the immunosuppressant cyclosporin and some of its analogs, adenine nucleotides, and the adenine nucleotide transporter inhibitor bongkrekic acid (Zoratti and Szabo, 1995). Mitochondrial swelling as measured by changes in absorbance has typically been studied in mitochondria after loading. High loads alone, or lower plus phosphate, uncoupler, or pro-oxidants, initiates transition, a process thought to propagate through the mitochondrial population (Bernardi, 1992; Broekemeier et al., 1989). When ruthenium red (RR) is added after to prevent its loss through reverse operation of the uniporter, application of
We have found that the incidence of functionally connected neuron‐myotube pairs in chick ciliary‐... more We have found that the incidence of functionally connected neuron‐myotube pairs in chick ciliary‐myotube cultures increases from 58% to more than 90% when the cells are treated for several hours with 8‐bromo‐cyclic adenosine monophosphate (8‐br‐cAMP) or with agents known to increase intracellular cAMP. The increase in connectivity was not accompanied by a change in neuron survival, or in the length of neurite‐myotube contact. Moreover, there was no change in the shape of the presynaptic action potential, in mean end plate potential (epp) amplitude or in the sensitivity of postsynaptic acetylcholine receptors (AChRs). One interpretation of these results is that a cAMP‐dependent phosphorylation acts as a trigger to activate a previously “silent” synapse.
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Papers by Janet Dubinsky