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Predominant Distribution of Nifedipine-Insensitive, High Voltage–Activated Ca 2+ Channels in the Terminal Mesenteric Artery of Guinea Pig
- Source :
- Circulation Research. 85:596-605
- Publication Year :
- 1999
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1999.
-
Abstract
- Abstract —We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-dependent Ca 2+ channels (current, NI- I Ca ) with unique biophysical and pharmacological properties in the terminal branches of guinea pig mesenteric artery, by using a whole-cell mode of the patch-clamp technique. The fraction of NI- I Ca appeared to increase dramatically along the lower branches of mesenteric artery, amounting to almost 100% of global I Ca in its periphery. With 5 mmol/L Ba 2+ as the charge carrier, NI- I Ca was activated with a threshold of −50 mV, peaked at −10 mV, and was half-activated and inactivated at −11 and −52 mV, respectively, generating a potential range of constant activation near the resting membrane potential. The NI- I Ca was rundown resistant, was not subject to Ca 2+ -dependent inactivation, and exhibited the pore properties typical for high voltage–activated Ca 2+ channels; Ba 2+ is ≈2-fold more permeable than Ca 2+ , and Cd 2+ is a better blocker than Ni 2+ (IC 50 , 6 and 68 μmol/L, respectively). Relatively specific blockers for N- and P/Q-type Ca 2+ channels such as ω-conotoxins GVIA and MVIIC (each 1 μmol/L) and ω-agatoxin IVA (1 μmol/L) were ineffective at inhibiting NI- I Ca , whereas nimodipine partially (10 μmol/L; ≈40%) and amiloride potently (≈75% with 1 mmol/L; IC 50 ; 107 μmol/L) blocked the current. Although these properties are reminiscent of R-type Ca 2+ channels, expression of the α 1E mRNA was not detected using reverse transcriptase–polymerase chain reaction. These results strongly suggest the predominant presence of NI, high voltage–activated Ca 2+ channels with novel properties, which may be abundantly expressed in peripheral small arterioles and contribute to their tone regulation.
- Subjects :
- Male
Nifedipine
Cations, Divalent
Physiology
Guinea Pigs
Drug Resistance
chemistry.chemical_element
Calcium
Guinea pig
Arteriole
medicine.artery
medicine
Animals
Tissue Distribution
Nimodipine
Membrane potential
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
Electric Conductivity
Anatomy
Calcium Channel Blockers
Molecular biology
Mesenteric Arteries
Amiloride
Electrophysiology
Kinetics
Female
Calcium Channels
Cardiology and Cardiovascular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....818d168028376509f2fae7084262e871