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Alpha-conotoxin-PnVIIA, an alpha-carboxyglutamate-containing peptide agonist of neuronal pacemaker cation currents, was characterized from the venom of the molluscivorous snail Conus pennaceus from specimens obtained in the northern Red Sea. The PnVIIA stimulates depolarization and action potential burst in the caudodorsal neurons of Lymnaea. The results were attributed to the enhanced slow inward cation current that may underly the neuron's bursting activity. The PnVIIA may thus serve as a prototype of a conotoxin class called alpha-conotoxins.

The venom of the molluscivorous snail Conus textile produces a hydrophobic omega-conotoxin-TxVII that affects dihydropyridine (DHP)-sensitive calcium channels. Amino acid sequence analysis reveals similarities to the cysteine framework of omega-conotoxins but the peptide is highly hydrophobic and has a negative charge. The toxin has no influence on sodium and potassium channels in caudodorsal cells. TxVII blocks the slowly inactivating DHP-sensitive calcium channel though it has no action on the fast inactivating channel.

Two conotoxins obtained from the venom of molluscivorous snail Conus pennaceus, PnIVA and PnIVB, block the sodium channels in the neurons of molluscs but are ineffective on the sodium channels in bovine chromaffin cells and rat brain synaptosomes. The amino acid sequences of the conotoxins reveal the presence of a cysteine framework, hence the nomenclature IV is used. Peptide toxins from snail venom are small and fall into pharmacological or chemical groups based on structure and activities on target receptors.

A new set of conotoxins extracted from the venom of Conus marmoreus and Lymnaea stagnalis (fresh water snail) behave indifferently towards both sodium and calcium currents. These toxins inhibit the function of voltage dependent sodium currents and fast-inactivating calcium current in snail neurons, by blocking them. The block of calcium current can be reversed quickly while the recovery of sodium current demands extensive wash. Both conotoxins allow extensive studies on sodium and L-type calcium channels in a voltage regulated environment.

Gonadal steroid feedback to oxytocin neurons during pregnancy is in part mediated via the neurosteroid allopregnanolone (3[Alpha]-OH-DHP), acting as allosteric modulator of postsynaptic [Gamma]-aminobutyric acid type A ([GABA.sub.A]) receptors. We describe here a form of nongenomic progesterone signaling by showing that 3[Alpha]-OH-DHP not only potentiates [GABA.sub.A] receptor-channel activity but also prevents its modulation by protein kinase C (PKC). Application of oxytocin or stimulation of PKC suppressed the postsynaptic GABA responses of oxytocin neurons in the absence, but not in the presence of 3[Alpha]-OH-DHP. This finding was true at the juvenile stage and during late pregnancy, when the [GABA.sub.A] receptor is sensitive to 3[Alpha]-OH-DHP. In contrast, after parturition, when the [GABA.sub.A] receptors expressed by oxytocin neurons are less sensitive to 3[Alpha]-OH-DHP, this neurosteroid no longer counteracts PKC. The change in [GABA.sub.A]-receptor responsiveness to 3[Alpha]-OH-DHP helps to explain the onset of firing activity and thus the induction of oxytocin release at parturition.