BK Channels in the Central Nervous System.

Large conductance Ca(2+)- and voltage-activated K(+) (BK) channels are widely distributed in the postnatal central nervous system (CNS). BK channels play a pleiotropic role in regulating the activity of brain and spinal cord neural circuits by providing a negative feedback mechanism for local increases in intracellular Ca(2+) concentrations. In neurons, they regulate the timing and duration of K(+) influx such that they can either increase or decrease firing depending on the cellular context, and they can suppress neurotransmitter release from presynaptic terminals. In addition, BK channels located in astrocytes and arterial myocytes modulate cerebral blood flow. Not surprisingly, both loss and gain of BK channel function have been associated with CNS disorders such as epilepsy, ataxia, mental retardation, and chronic pain. On the other hand, the neuroprotective role played by BK channels in a number of pathological situations could potentially be leveraged to correct neurological dysfunction.

Disrupted reproduction, estrous cycle, and circadian rhythms in female mice deficient in vasoactive intestinal peptide.

The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP)-expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle, but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produce about half the offspring of their wild-type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle; that is, ovulation occurs less frequently and results in the release of fewer oocytes compared with controls. Circadian rhythms of wheel-running activity are disrupted in the female mutant mice, as is the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibits lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator, which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success.

Platelet function analysis in children with Schönlein-Henoch syndrome.

BACKGROUND: Schönlein-Henoch syndrome (SHS) or anaphylactic purpura in childhood is the result of pathologic and immunologic responses to different antigens. These antigens could induce the formation of immune complexes responsible for vasculitis and their precipitation on the endothelium of small blood vessels. Purpuric bruises, hematuria, hematemesis, melena, or hematochesis may suggest coagulation disturbances. Increasing bleeding tendency may suggest platelet function disturbance. To examine the qualitative function of platelets in children with SHS, we decided to analyze its aggregation function. METHODS: Using the Born method of testing, we analyzed platelet aggregation in 24 children with SHS. RESULTS: Based on the aggregograms examined, we observed that most patients had abnormal aggregation curves, in which platelets demonstrated a block of release of the endogenous ADP, with or without disaggregation. CONCLUSIONS: One clinical symptom of SHS appearing in most patients is a mild or increased tendency toward bleeding. On measuring induced aggregation of platelets in children with SHS, we observed that the qualitative function of platelets was disturbed.