Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6.

Animal peptide toxins have become powerful tools to study structure-function relationships and physiological roles of voltage-activated Ca(2+) channels. In the present study, we investigated the effects of PnTx3-6, a neurotoxin purified from the venom of the spider Phoneutria nigriventer on cloned mammalian Ca(2+) channels expressed in human embryonic kidney 293 cells and endogenous Ca(2+) channels in N18 neuroblastoma cells. Whole-cell patch-clamp measurements indicate that PnTx3-6 reversibly inhibited L-(alpha(1C)/Ca(v)1.

Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin.

Pyrethroids are commonly used insecticides for both household and agricultural applications. It is generally reported that voltage-gated sodium channels are the primary target for toxicity of these chemicals to humans. The phylogenetic and structural relatedness between sodium channels and voltage-gated calcium (Ca) channels prompted us to examine the effects of the type 1 pyrethroid allethrin on the three major classes of mammalian calcium channels exogenously expressed in human embryonic kidney 293 cells.

Differential inhibition of T-type calcium channels by neuroleptics.

T-type calcium channels play critical roles in cellular excitability and have been implicated in the pathogenesis of a variety of neurological disorders including epilepsy. Although there have been reports that certain neuroleptics that primarily target D2 dopamine receptors and are used to treat psychoses may also interact with T-type Ca channels, there has been no systematic examination of this phenomenon. In the present paper we provide a detailed analysis of the effects of several widely used neuroleptic agents on a family of exogenously expressed neuronal T-type Ca channels (alpha1G, alpha1H, and alpha1I subtypes).

Molecular and functional characterization of a family of rat brain T-type calcium channels.

Voltage-gated calcium channels represent a heterogenous family of calcium-selective channels that can be distinguished by their molecular, electrophysiological, and pharmacological characteristics. We report here the molecular cloning and functional expression of three members of the low voltage-activated calcium channel family from rat brain (alpha(1G), alpha(1H), and alpha(1I)). Northern blot and reverse transcriptase-polymerase chain reaction analyses show alpha(1G), alpha(1H), and alpha(1I) to be expressed throughout the newborn and juvenile rat brain.

alpha 1B N-type calcium channel isoforms with distinct biophysical properties.

N-type calcium channels both generate the initial calcium signal to trigger neurotransmitter release and also interact with synaptic release proteins at many mammalian central nervous system synapses. Two isoforms of the alpha 1B N-type channel from rat brain (alpha 1B-I and alpha 1B-II) were found to differ in four regions: (1) a glutamate (Glu) to glycine (Gly) substitution in domain I S3; (2) a Gly to Glu substitution in the domain I-II linker; (3) the insertion or deletion of an alanine (Ala) in the domain I-II linker; and (4) the presence or absence of serine/phenylalanine/methionine/glycine (SFMG) in the linker between domain III S3-S4. Comparison of the electrophysiological properties of the alpha 1B-I and alpha 1B-II N-type channels shows that they exhibit distinct kinetics as well as altered current-voltage relations.