Locus coeruleus (LC) neurons in brain slices from adult rats were studied using intracellular and extracellular recordings to investigate synchronous activity. Spontaneous field potentials were recorded with extracellular electrodes in solutions containing tetraethylammonium chloride (10 mM) and BaCl 2 (1 mM). These field potentials were found throughout but not outside the LC cell body region. No field potentials were observed in control solutions. Paired recordings showed that field potentials were synchronous in all areas of the LC. The synchronous activity was resistant to tetrodotoxin (1 M) and to the neurotransmitter receptor blockers D-2-amino-5-phosphonopentanoic acid, bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, idazoxan, and strychnine, suggesting that this activity was not synaptically driven. Field potentials were also synchronous with oscillations in membrane potential recorded with intracellular electrodes. The oscillations in membrane potential were 5-30 mV in amplitude and had a biphasic waveform. Neither the frequency nor the waveform of the oscillations was dependent on the membrane potential. The glycyrrhetinic acid derivative carbenoxolone and intracellular acidification with CO 2 disrupted synchronous activity, suggesting a role of electrotonic coupling. When the cell body region of the LC was isolated from the pericoerulear dendritic regions by sectioning the slice rostral and caudal to the cell body region, synchronous activity was reduced or abolished. Dendritic interaction in the pericoerulear region was also indicated by improved voltage control of the opioid-induced potassium current, as indicated by a shift in the reversal potential to the potassium equilibrium potential. The results suggest that electrical interactions between dendrites outside the cell body region can account for synchronous activity within the nucleus.

No abstract

Activities of superoxide dismutase (SOD) and lipid peroxide (LPO) were studied in corpora lutea of pregnant rats. SOD activities, both Mn-SOD and Cu,Zn-SOD, gradually increased in the corpora lutea until day 15 of pregnancy and decreased thereafter until day 21 of pregnancy, in a similar manner to serum progesterone concentration. LPO activities remained low until day 15 of pregnancy, but increased rapidly after day 15 to day 21 of pregnancy. Incubation of the dispersed luteal cells from day 15 of pregnancy in vitro showed that FeSO4 and ascorbic acid, which induce lipid peroxidation, significantly inhibited progesterone secretion. The inhibitory effects of FeSO4 and ascorbic acid were blocked by the simultaneous addition of alpha-tocopherol. These results suggest important roles for SOD and LPO in regulating luteal function during pregnancy.

No abstract

Mechanical unloading increases functional sarcoplasmic reticulum Ca(2+) ATPase and improves [Ca(2+)](i) handling and contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial effects of mechanical unloading were not observed in normal hearts.

Effects of methylphenidate (MPH), a therapeutic agent used in children presenting the attention deficit hyperactivity disorder (ADHD), on the membrane potential and current in neurons of the rat locus coeruleus (LC) were examined using intracellular and whole cell patch-clamp recording techniques. Application of MPH (30 microM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response with amplitude of 12 +/- 1 mV (n = 29). Spontaneous firing of LC neurons was blocked during the MPH-induced hyperpolarization. Superfusion of LC neurons with ACSF containing 0 mM Ca(2+) and 11 mM Mg(2+) (Ca(2+)-free ACSF) produced a depolarizing response associated with an increase in spontaneous firing of the action potential. The MPH-induced hyperpolarization was blocked in Ca(2+)-free ACSF. Yohimbine (1 microM) and prazosin (10 microM), antagonists for alpha(2) and alpha(2B/2C) receptors, respectively, blocked the MPH-induced hyperpolarization in LC neurons. Tetrodotoxin (TTX, 1 microM) produced a partial depression of the MPH-induced hyperpolarization in LC neurons. Under the whole cell patch-clamp condition, MPH (30-300 microM) produced an outward current (I(MPH)) with amplitude of 110 +/- 6 pA (n = 17) in LC neurons. The I(MPH) was blocked by Co(2+) (1 mM). During prolonged application of MPH (300 microM for 45 min), the hyperpolarization gradually decreased in the amplitude and eventually disappeared, possibly because of depression of norepinephrine (NE) release from noradrenergic nerve terminals. At a low concentration (1 microM), MPH produced no outward current but consistently enhanced the outward current induced by NE. These results suggest that the MPH-induced response is mediated by NE via alpha(2B/2C)-adrenoceptors in LC neurons. I(MPH) was associated with an increase in the membrane conductance of LC neurons. The I(MPH) reversed its polarity at -102 +/- 6 mV (n = 8) in the ACSF. The reversal potential of I(MPH) was changed by 54 mV per decade change in the external K(+) concentration. Current-voltage relationship showed that the I(MPH) exhibited inward rectification. Ba(2+) (100 microM) suppressed the amplitude and the inward rectification of the I(MPH.) These results suggest that the I(MPH) is produced by activation of inward rectifier K(+) channels in LC neurons.

No abstract

No abstract