Cortical axons contain a diverse range of voltage-activated ion channels, including Ca(2+) currents. Interestingly, Ca(2+) channels are not only located at presynaptic terminals, but also in the axon initial segment (AIS), suggesting a potentially important role in the regulation of action potential generation and neuronal excitability. Here, using two-photon microscopy and whole-cell patch-cla...

Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved in kidney function. It was hypothesized that human renal vascular excitation-contraction coupling involve...

      In order to investigate the effects of dimethylamino substituent at postion 2 of the dihydropyridine nucleus on its activity, dialkyl 1,4-dihydro-2-[2-(dimethy- lamino) ethyl]-6-methyl-4-(1-benzyl-2-alkylthio-5-imidazolyl)-3,5-pyrdinedicar- boxylates (6a-f) were synthesized. The synthesis was started from dialkyl 1,4- dihydro-2,6-dimethyl-4-(1-benzyl-2-alkylthio-5-imidazolyl)-3,5-pyridine...

In order to investigate the effects of dimethylamino substituent at position 2 of the dihydropyridine nucleus on activity, starting from dialkyl l ,4-dihydro-2,6-dimethyl-4- (l-benzyl-2-alkylthio-5-imidazolyl)-3,5-pyridinedicarboxylates (5a-f) which their synthesis and effects as calcium channel antagonist on guinea-pig ileum has been reported previously, dialkyl l,4-dihydro-2-[2-(dimethyla...

There is a clear need for new therapeutics to treat alcoholism. Here, we test our hypothesis that selective inhibitors of neuronal calcium channels will reduce ethanol consumption and intoxication, based on our previous studies using knock-out mice and cell culture systems. We demonstrate that pretreatment with the novel mixed N-type and T-type calcium channel antagonist 1-(6,6-bis(4-fluorophen...

Pharmacotherapeutic options for pulmonary arterial hypertension (PAH) have increased dramatically in the last two decades and along with this have been substantial improvements in survival. Despite these advances, however, PAH remains a progressive and ultimately fatal disease for most patients and only epoprostenol has been shown to improve survival in a randomized control trial. Clinical obse...

BACKGROUND Although intention-to-treat analysis is a standard approach, additional supplemental analyses are often required to evaluate the biological relationship among interventions, intermediates, and outcomes. Therefore, we need to evaluate whether the effect of an intervention on a particular outcome is mediated by a hypothesized intermediate variable. PURPOSE To evaluate the size of the...

OBJECTIVES Combination therapy using an angiotensin II receptor blocker is expected to promote medication adherence and alleviate economic burden among patients by reducing the number of drugs taken, and thereby to lower associated medical costs. In the present retrospective study, we conducted a survey on the use of angiotensin II receptor blocker-containing combination tablets as anti-hyperte...

  The involvement of NMDA receptors and voltage-dependent calcium channels in augmentation of long-term potentiation (LTP) was investigated at the Schaffer collateral CA1 pyramidal cell synapses in hippocampal slices of morphine dependent rats, using primed-burst tetanic simulation. The amplitude of the population spike and its delay were measured as indices of increase in postsynaptic excitabi...