The geniculate ganglion, which provides innervation to taste buds in the anterior tongue and palate, is unique among sensory ganglia in that its neurons depend on both neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) for survival. Whereas BDNF is additionally implicated in taste axon guidance at targeting stages, much less is known about the guidance role of NT4 during targeting, or about either neurotrophin during initial pathfinding. NT4 and BDNF have distinct expression patterns in vivo, raising the possibility of distinct roles. We characterized the influence of NT4 and BDNF on geniculate neurites in collagen I gels at early embryonic through postnatal stages. During early pathfinding to the tongue (embryonic days 12–13; E12–13), NT4 and BDNF promote significantly longer outgrowth than during intralingual targeting (E15–18). NT4 is more potent than BDNF at stimulating neurite outgrowth and both factors exhibit concentration optima, i.e. intermediate concentrations (0.25 ng/ml NT4 or 25 ng/ml BDNF) promote maximal neurite extension and high concentrations (10 ng/ml NT4 or 200 ng/ml BDNF) suppress it. Only partial suppression was seen at E12 (when axons first emerge from the ganglion in vivo) and postnatally, but nearly complete suppression occurred from E13 to E18. We show that cell death is not responsible for suppression. Although blocking the p75 receptor reduces outgrowth at the optimum concentrations of NT4 and BDNF, it did not reduce suppression of outgrowth. We also report that NT4, like BDNF, can act as a chemoattractant for geniculate neurites, and that the tropic influence is strongest during intralingual targeting (E15–18). NT4 does not appear to act as an attractant in vivo, but it may prevent premature invasion of the epithelium by suppressing axon growth.

Four phases (0 to 3) were defined kinetically for potassium in the dog papillary muscle when perfused arterially for four to five hours with solution containing 4 mM/liter K + . Total tissue K + fell from 91.1±1.99 to 41.0±1.06 mmoles/liter after three hours perfusion. It then remained stable during the period when kinetic studies were done. The mean rate constant λ (min -1 ), potassium content (mmoles/liter tissue water) and suggested origin of each phase are respectively: (phase 0) λ 0 = 3.2, 0.3, vascular; (phase 1) λ 1 = 0.65, 2.06, interstitial; (phase 2) λ 2 = 0.0139, 39.3, intracellular; (phase 3) λ 3 < 0.004, <0.5, origin unknown. Alteration of K + concentration in perfusing fluid produced significant changes in the intracellular exchange rate of K + . This was in marked contrast to increments in frequency of contraction which had no effect on the overall exchangeability of intracellular potassium. Increases in rate, however, were associated with a transient net loss of intracellular K + . This loss continued if the active tension of the muscle declined and if contracture progressed. The loss ceased if muscle function remained stable during continued increased frequency of contraction. A positive tension staircase was approximately proportional to the net K + loss. The net K + loss was 0.93 mmole/liter tissue water in nine muscles in which a mean 27 beats/min rate increment was introduced for a mean of 16 minutes. This represented 2.4% of intracellular K + . A significant time lag was found before the net K + loss reached a maximum rate and began to decline. This is compared with the previously demonstrated transient net increment in Ca ++ uptake that accompanies increased frequency of contraction. These ionic movements are consistent with the theory that Na + movements in and out of a "specialized membrane region" are related to Ca ++ movements and thereby influence the control of myocardial contractility.

A significant number of patients suffering from traumatic brain injury (TBI) have a high blood alcohol level at the time of injury. Furthermore, drinking alcohol in a binge-like pattern is now recognized as a national problem, leading to a greater likelihood of being injured. Our objective was to determine the consequences of a binge paradigm of alcohol intoxication at the time of TBI on long-term functional outcome using a sensitive test of sensorimotor function. We trained adult, male, Sprague Dawley rats on the skilled forelimb reaching task and then administered a single binge dose of ethanol (2g/kg, i.p.) or saline for three consecutive days (for a total of 3 doses). One hour after the final ethanol dose, rats underwent a TBI to the sensorimotor cortex corresponding to the preferred reaching forelimb. Animals were then tested for seven weeks on the skilled forelimb reaching task to assess the profile of recovery. We found that the group given ethanol prior to TBI displayed a slower recovery curve with a lower recovery plateau as compared to the control group. Therefore, even a relatively short (3 day) episode of binge alcohol exposure can negatively impact long-term recovery from a TBI, underscoring this significant public health problem.