title: Effect of catecholamines on the ventricular myocyte action potential in raised extracellular potassium.
abstract: We describe the relationship between catecholamines and raised extracellular potassium ([K+]o) on action potential parameters and calcium currents in isolated ventricular myocytes of the guinea-pig and relate these findings to the problem of understanding how the heart is protected from exercise-induced hyperkalaemia ([K+]a up to 8.5 mM). Action potential duration (APD90), amplitude and upstroke velocity were recorded in stimulated (2Hz) guinea-pig ventricular myocytes using whole-cell patch electrode recordings (37 degrees C). Cells were superfused with normal K+ Tyrode and with raised K+ Tyrode in the presence of either noradrenaline, adrenaline or raised calcium. Inward calcium current was measured using voltage clamp. Raised K+ (8, 12, 16 mM K+ Tyrode) caused a significant (P < 0.01) depolarisation, shortened the APD90 and decreased the action potential amplitude and upstroke velocity. In raised K+ Tyrode addition of noradrenaline (0.08-0.1 microM) or adrenaline (0.1-0.2 microM) increased action potential amplitude (P < 0.01), APD90 (P < 0.01) and upstroke velocity (P < 0.01) (measured only in 16 mM K+ Tyrode). In 12 mM K+ Tyrode raised Ca2+ (5-6 mM) increased action potential amplitude (P < 0.05) and shortened APD90 (P < 0.05). Addition of NA (0.08-0.1 microM) increased the inward Ca2+ current. All effects were fully reversible. In raised [K+]o increases in catecholamines and [Ca2+]o cause changes in action potential parameters that would be expected to maintain propagation of the cardiac action potential in the whole heart. Thus, in the ventricular myocyte the increase in conductance to Ca2+ caused by catecholamines may be one factor that is important in minimising the potentially adverse effects of exercise-induced hyperkalaemia.
authors.affiliation: University Laboratory of Physiology, Oxford, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Paterson
authors.forename: J
authors.initials: J
authors.lastname: Rogers
authors.forename: T
authors.initials: T
authors.lastname: Powell
authors.forename: H F
authors.initials: HF
authors.lastname: Brown
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D004837:Epinephrine / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*
chemical_list: D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine