Calcium influx via L-type (Cav1.2 and Cav1.3) calcium channels is tightly regulated to ensure optimal intracellular calcium levels. Although much is known about acute modulation of these channels by second messengers, the mechanisms that control their trafficking to and from the plasma membrane remain poorly understood. In this issue of Neuron, Green and colleagues demonstrate that the opening ...

Lead is a potent and reversible inhibitor of the voltage-dependent calcium current of Aplysia neurons in a concentration range (1-1000 microM) similar to that which elicits toxic effects in man. The threshold for inhibition is 1 microM and the dissociation constant about 90 microM. The inhibition is due to reduction of the peak current amplitude, and not due to alteration of the voltage depende...

BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity...

Cocaine use poses a major health problem not only because of the dependence it causes but also because of the generation of life-threatening cardiac arrhythmias following overdose. Elucidating the molecular mechanisms of action of cocaine, therefore, remains a critical step in developing treatment for cocaine addiction and preventing cardiac complications. Although the neurotransmitter transpor...

........................................................................................................................................ ii Acknowledgments ......................................................................................................................... iii List of Tables .......................................................................................................

In response to retinal disease and injury, the axon terminals of rod photoreceptors demonstrate dramatic structural plasticity, including axonal retraction, neurite extension, and the development of presynaptic varicosities. Cone cell terminals, however, are relatively inactive. Similar events are observed in primary cultures of salamander photoreceptors. To investigate the mechanisms underlyin...

Ion channels are interesting molecules since they mediate not only uterine contraction but also uterine relaxation. We have examined the expression, function, and correlation between the large conductance calcium-activated potassium (BKCa) channel, beta2 adrenoceptor (AR), and long-lasting (L) type calcium (Ca2+) channel. These are the main channels and receptor that are involved in the uterine...

GABA and norepinephrine inhibit high voltage-activated calcium current in chick sensory neurons. Using specific pharmacological tools, we have dissected this current into two components: the major one is omega-conotoxin sensitive and dihydropyridine resistant (N-type) while the minor one is dihydropyridine sensitively and omega-conotoxin resistant (L-type). The ability to selectively eliminate ...

The role of T-type Ca2+ channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca2+ channels in resistance arteries has been proposed to explain the effect of the antihypertensive drug mibefradil. In the present study, we used a third generation, time- and tissue-specific conditional knockout model of the L-type Ca2+ chann...