Both voltage-activated potassium channels and the concentration of free intracellular calcium have been implicated in the activation of T lymphocytes. Using the patch-clamp technique, we now show an unexpected relationship between the level of intracellular calcium [Ca]i in human lymphocytes and the amplitude of a voltage-dependent current: the elevation of [Ca]i decreases the potassium conductance. This is in contrast to other systems where [Ca]i activates K+ channels. Our results suggest that the level of intracellular calcium regulates the effective number of K+ channels capable of being activated.

Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Abeta25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca(2+) entry into neurons by about 20%, which is explained by their selective action on L-type Ca(2+) channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Abeta25-35 partially depends on inhibition of potential-dependent Ca(2+) entry.

Electrophysiological in situ recordings from pheromone-sensitive sensilla trichodea of Bombyx mori males with a recording pipette which contained G-protein-activating fluoride, showed receptor cell activity similar to that evoked by pheromone stimulation. This suggests that G-proteins might be physiologically active in olfactory sensilla of insects in situ. Biochemical experiments using specific antibodies revealed the presence of G-protein, belonging to the Gq family, in antennal preparations. Similar G-protein was identified in sensory hair preparations of Antheraea pernyi which contained only cuticle, sensillum lymph and dendritic material. Moreover, the absence of this G-protein in pure sensillum lymph preparations indicates its association with the receptive dendrites. This particular association could be shown by immunolabelling studies at the ultrastructural level. Strong specific labelling of membranes of receptor-cell dendrites was found in all types of olfactory sensilla present on the antenna of the silkmoths. Additional specific labelling of apical membranes of auxiliary cells, epidermal cells and membranes forming the axon/glia interface demonstrated that this G-protein is not restricted to the sensory dendrites and that other signal-transduction pathways could be present at these membranes. In summary, the experiments imply a participation of G-protein of the Gq family in signal transduction of olfactory receptor cells in moths.

Two proteins of the IP3 transduction pathway were identified by Western blots in homogenates of isolated pheromone-sensitive sensilla of the silkmoth Antheraea polyphemus. A 110 kDa protein was recognized by an antiserum raised against the Drosophila phospholipase C beta (PLC beta p121) and a 80kDa protein was labelled by an antiserum against a synthetic peptide of a conserved region of protein kinase C (PKC). Incubation of homogenized sensory hairs with the main sex pheromone component, (E,Z) 6-11 hexadecadienyl acetate, resulted in a 6-fold increase in the activity of PKC compared to controls without pheromone. In contrast, incubation with pheromone did not affect the activity of protein kinase A (PKA). Activation of PKC by the membrane permeable dioctanoylglycerol led to excitation of the pheromone-sensitive receptor neurons. These data support the current concept that pheromone perception of moths is mediated by the IP3 transduction pathway.

The effects of the membrane-permeable dibutyryl guanosine 3', 5'-cyclic monophosphate (db-cGMP) on the bombykol-elicited receptor current and nerve impulse activity were studied using the open sensillum recording technique. db-cGMP was applied to the outer dendritic membrane of the olfactory receptor neuron of the moth Bombyx mori. db-cGMP reduced the amplitude of the overall receptor current activated by a pulse of strong pheromone stimuli as well as diminished the nerve impulse frequency elicited by continuously applied weak pheromone stimuli. The observed inhibition of the response to pheromone was due to size reduction of an elementary receptor current that elicits the nerve impulses and underlies the overall receptor current. It is suggested that cGMP is a factor which may adjust cell sensitivity to odour and play a role in olfactory adaptation.