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Enhancement of ATP‐sensitive potassium current in cat ventricular myocytes by beta‐adrenoreceptor stimulation.
Author(s) -
Schackow T E,
Ten Eick R E
Publication year - 1994
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1994.sp020008
Subject(s) - isoprenaline , chemistry , stimulation , medicine , endocrinology , membrane potential , cholera toxin , intracellular , pertussis toxin , propranolol , biophysics , agonist , biochemistry , biology , receptor , g protein
1. To address the questions of whether beta‐adrenoreceptor stimulation can augment ATP‐sensitive potassium current (IK(ATP)), and what the mechanism of such an effect might be, action potentials and whole‐cell ionic currents were recorded from adult cat cardiac ventricular myocytes using a conventional whole‐cell patch technique. 2. An outwardly directed, ohmic, non‐inactivating, glyburide (10 microM)‐sensitive current reversing near the reversal potential for potassium (EK) developed slowly (10‐25 min) in cells dialysed with an ATP‐free pipette (intracellular) solution. During this time, action potential duration markedly decreased while the resting membrane potential hyperpolarized closer to EK. Extended (> 30 min) periods of internal dialysis with ATP‐free solution eventually resulted in run‐down of the outward current. 3. Externally applied isoprenaline (1 microM) caused a rapidly developing (< or = 60 s), sustained enhancement of a glyburide (10 microM)‐sensitive IK(ATP) in cells internally dialysed with ATP‐free solution. IK(ATP) remained elevated even after the isoprenaline was removed, and subsequent applications of the beta‐agonist failed to increase IK(ATP) further. Half‐maximal isoprenaline stimulation of IK(ATP) occurred at a concentration of approximate of 1.5 nM. 4. Pretreatment with propranolol (1 microM) prevented the enhancement of IK(ATP) by a beta‐agonist. 5. Isoprenaline‐induced IK(ATP) could be blocked by either internal application of GDP‐beta‐S (2‐5 mM) or pretreatment with cholera toxin (1‐10 microgram ml‐1, > 18 h). Pretreatment with pertussis toxin (1‐2 microgram ml‐1, > 18 h) did not attenuate the isoprenaline response, whereas internally applied GTP‐gamma‐S (100 microM) or F‐ (20 mM) caused IK(ATP) to increase rapidly in the absence of the beta‐agonist. 6. Although externally applied forskolin (10 microM) also stimulated IK(ATP), neither 1,9‐dideoxyforskolin (10 microM) nor 8‐(4‐chlorophenylthio)‐cAMP (200 microM) had any effect on the current. Internal application of the adenylate cyclase inhibitor 2'‐deoxyadenosine‐3'‐monophosphate (100 microM) resulted in a reduction in the response to isoprenaline, while internal application of a protein kinase A inhibitor (PKI5‐24, 22.5 microM) did not attenuate the response to the beta‐agonist. 7. IK(ATP) developed slowly during internal dialysis with ATP‐free solution.(ABSTRACT TRUNCATED AT 400 WORDS)