Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs.

نویسندگان

  • B P Bean
  • M Sturek
  • A Puga
  • K Hermsmeyer
چکیده

The patch clamp technique was used to make whole-cell recordings of calcium channel currents from single muscle cells freshly isolated from rat mesenteric arteries. The cells were found to contain two types of calcium channels; one type is activated by small depolarizations and inactivates quickly, whereas the other requires stronger depolarizations for activation and inactivates more slowly. Nitrendipine blocked the second type of channels with a potency that depended on membrane potential. Interpreted by a modulated receptor hypothesis, these results suggest that nitrendipine binds to the inactivated state of the channel with a KD of about 0.5 nM, similar to concentrations effective in relaxing blood vessels. The magnitude of the calcium channel current was small compared with other excitable cells, but the "calcium agonist" drug BAY K8644 produced a 10-fold augmentation of calcium channel current, suggesting the existence of a large "reserve" of calcium channel current.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Synthesis and Biological Evaluation of New Tricyclic Dihydropyridine Based Derivatives on Potassium Channels

The present study reports a microwave-assisted method for the synthesis of twelve novel tricyclic 1,4-dihydropyridine derivatives in which dimethyl-substituted cyclohexane and / or tetrahydrothiophene rings are fused to the DHP ring. The structures of the compounds were confirmed by spectral methods and elemental analysis. The potassium channel opening effects of the compounds were determined o...

متن کامل

The vasodilatory action of telmisartan on isolated mesenteric artery rings from rats

Objective(s): Angiotensin Ⅱ type 1 receptor blockers (ARBs) represent one of the widely used antihypertensive agents. In addition to anti-hypertension effect, some ARBs also show other molecular effects such as activating peroxisome proliferator-activated receptor-γ and so on. Here we studied the effects of telmisartan on the rat isolated mesenteric artery rings pre-contracted by phenylephrine ...

متن کامل

Upregulation of L-Type Ca Channels in Mesenteric and Skeletal Arteries of SHR

An increased Ca influx attributed to dihydropyridine-sensitive L-type Ca channels has been demonstrated in mesenteric vascular smooth muscle cells of spontaneously hypertensive rats (SHR). This study examined whether an upregulation of the pore-forming 1C subunit of the L-type Ca 2 channel underlies this ionic defect. With the use of mesenteric arcade arteries from 12to 16-week-old SHR and norm...

متن کامل

Effects of two new dihydropyridine derivatives, mepudipine and dibudipine, on isolated human internal mammary artery and rat left atrium

  Among the present classes of calcium channel blockers, dihydropyridine derivatives are widely used in the therapy of hypertension, angina pectoris and the other cardiovascular diseases. Since the prototype of dihydropyridine derivatives, nifedipine, does not have the optimum pharmacokinetic and pharmacodynamic characteristics, several attempts have been made to synthesize other drugs in this ...

متن کامل

Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

Objective(s) Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT') and L-type calcium channels were investigated on isolated rat aorta. Materials and Methods Aortic rings were pre-contracted with 1 pM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Circulation research

دوره 59 2  شماره 

صفحات  -

تاریخ انتشار 1986