Pharmacology of the high-affinity apamin receptor in rabbit heart

John Schetz, Peter A.V. Anderson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Apamin is a potent blocker of calcium-activated small conductance potassium (SK) channels in neurons, liver, skeletal muscle and ileum smooth muscle, but not in cardiac muscle. Cardiac muscle is devoid of SK channels; however, in isolated, single ventricular myocytes apamin is an extremely potent blocker of the L-type calcium current, and the anti-arrhythmic drug quinidine reverses apamin block. Objective: To characterize the receptor binding properties and pharmacology of the apamin receptor in heart. Methods: The binding properties of the apamin receptor were determined by rapid filtration of purified rabbit heart membranes. Results: Monoiodinated apamin binds to a labile, membrane-bound protein in heart membranes at a single, high-affinity site (KD = 8.07 ± 2.14 pM and Bmax = 686 ± 167 fmoles/mg protein, significant run test at P = 0.05 for a one site fit).125I-apamin binding is dose-dependently inhibited by apamin, scyllatoxin, quinidine, amiloride, as well as a variety of di- and trivalent cations that are classical blockers of L-type calcium channels (e.g. Co2+, Cd2+, Mn2+, La3+, Gd3+). The cardiac apamin receptor is also critically dependent upon pH, temperature and KCl, and co-purifies in the same membrane fraction as L-type cardiac Ca2+ channels. Conclusions: The apamin receptor in rabbit heart P2 membranes has pharmacological and biochemical properties in common with both an SK channel and an L-type Ca2+ channel.

Original languageEnglish
Pages (from-to)755-762
Number of pages8
JournalCardiovascular Research
Volume30
Issue number5
DOIs
StatePublished - 1 Jan 1995

Fingerprint

Apamin
Pharmacology
Rabbits
Quinidine
Membranes
Small-Conductance Calcium-Activated Potassium Channels
Myocardium
L-Type Calcium Channels
Amiloride
Anti-Arrhythmia Agents
Divalent Cations
Ileum
Muscle Cells
Smooth Muscle
apamin receptor
Membrane Proteins
Skeletal Muscle
Calcium
Neurons
Temperature

Keywords

  • Apamin
  • Apamin receptor
  • Calcium channels
  • Potassium channel
  • Quinidine
  • Rabbit, ventricular myocytes
  • SK

Cite this

Schetz, John ; Anderson, Peter A.V. / Pharmacology of the high-affinity apamin receptor in rabbit heart. In: Cardiovascular Research. 1995 ; Vol. 30, No. 5. pp. 755-762.
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Pharmacology of the high-affinity apamin receptor in rabbit heart. / Schetz, John; Anderson, Peter A.V.

In: Cardiovascular Research, Vol. 30, No. 5, 01.01.1995, p. 755-762.

Research output: Contribution to journalArticle

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AU - Anderson, Peter A.V.

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AB - Apamin is a potent blocker of calcium-activated small conductance potassium (SK) channels in neurons, liver, skeletal muscle and ileum smooth muscle, but not in cardiac muscle. Cardiac muscle is devoid of SK channels; however, in isolated, single ventricular myocytes apamin is an extremely potent blocker of the L-type calcium current, and the anti-arrhythmic drug quinidine reverses apamin block. Objective: To characterize the receptor binding properties and pharmacology of the apamin receptor in heart. Methods: The binding properties of the apamin receptor were determined by rapid filtration of purified rabbit heart membranes. Results: Monoiodinated apamin binds to a labile, membrane-bound protein in heart membranes at a single, high-affinity site (KD = 8.07 ± 2.14 pM and Bmax = 686 ± 167 fmoles/mg protein, significant run test at P = 0.05 for a one site fit).125I-apamin binding is dose-dependently inhibited by apamin, scyllatoxin, quinidine, amiloride, as well as a variety of di- and trivalent cations that are classical blockers of L-type calcium channels (e.g. Co2+, Cd2+, Mn2+, La3+, Gd3+). The cardiac apamin receptor is also critically dependent upon pH, temperature and KCl, and co-purifies in the same membrane fraction as L-type cardiac Ca2+ channels. Conclusions: The apamin receptor in rabbit heart P2 membranes has pharmacological and biochemical properties in common with both an SK channel and an L-type Ca2+ channel.

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