BACKGROUND/AIMS Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium channels in A7r5 rat aortic vascular smooth muscle cells. METHODS L-type calcium channel currents were recorded by a patch-clamp technique. The mRNA expression of CaV1.2 was determi...

It is now clear that the wide variety of neuronal voltage-dependent calcium channels (Table 1) are determinants of transmitter release (N-type, P-type, Q-type channels), repetitive or burst neuronal firing (T-type channels) and perhaps of some aspects of gene expression (L-type channels). However, although the calcium overload hypothesis of neuronal cell death has been around for 14 years, ther...

Two for T Minireview other is more unexpected: a report that the already-known ␣ 1B , ␣ 1C , and ␣ 1E clones can produce single channel activity with many similarities to T-type channels Harvard Medical School Boston, Massachusetts 02115 (Meir and Dolphin, 1998). Perez-Reyes and colleagues identified the new clone by screening GenBank expressed sequence tags (ESTs) for homology to existing ␣ 1 ...

Two voltage-gated calcium channel subtypes-CaV1.2 and CaV1.3-underlie the major L-type Ca(2+) currents in the mammalian central nervous system. Owing to their high sequence homology, the two channel subtypes share similar pharmacological properties, and at high doses classic calcium channel blockers, such as dihydropyridines, phenylalkylamines and benzothiazepines, do not discriminate between t...

L-type calcium channels are present in most electrically excitable cells and are needed for proper brain, muscle, endocrine and sensory function. There is accumulating evidence for their involvement in brain diseases such as Parkinson disease, febrile seizures and neuropsychiatric disorders. Pharmacological inhibition of brain L-type channel isoforms, Cav1.2 and Cav1.3, may therefore be of ther...

Low-voltage-activated (T-type) calcium channels are important regulators of the transmission of nociceptive information in the primary afferent pathway and finding ligands that modulate these channels is a key focus of the drug discovery field. Recently, we characterized a set of novel compounds with mixed cannabinoid receptor/T-type channel blocking activity and examined their analgesic effect...

A protein that imitates the sequence of a highly conserved segment predicted to line the pore of dihydropyridine-sensitive L-type calcium channels was designed and synthesized. Single-channel conductance properties were studied in planar lipid bilayers. The synthetic protein emulates the ionic conductance, ionic selectivity, and pharmacological properties of the authentic calcium channel, inclu...

Insulin-like growth factor-1 (IGF-1) promotes the survival of cerebellar granule neurons by enhancing calcium influx through L-type calcium channels, whereas NMDA receptor-mediated calcium influx can lead to excitotoxic death. Here we demonstrate that L and NMDA receptor channel activities differentially regulate the transcription factor C/EBPbeta to control neuronal survival. Specifically, we ...