Voltage dependence of beta-adrenergic modulation of conduction in the canine Purkinje fiber.
Although recent voltage-clamp and microelectrode studies have demonstrated beta-adrenergic modulation of Na+ current (INa) the modulation of conduction by catecholamines and the voltage dependence of that process have not been elucidated. To determine whether voltage-dependent modulation of conduction occurs in the presence of a beta-adrenergic agonist, the effect of 1 mumol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K+]o 5.4 mmol/L), isoproterenol increased squared conduction velocity [theta 2, 0.39 +/- 0.25 (m/s)2 (mean +/- SD)] from 3.46 +/- 0.86 to 3.85 +/- 0.98 (m/s)2 (P < .011), an 11% change, without altering the maximum first derivative of the upslope of phase 0 of the action potential (Vmax, 641 +/- 50 versus 657 +/- 47 V/s, P = NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K+]o titration, theta 2 declined 79% to 0.73 +/- 0.44 (m/s)2 as Vmax decreased 85% to 95 +/- 43 V/s (P < .02). The addition of isoproterenol further decreased theta 2 to 0.49 +/- 0.33 (m/s)2 (P = .02) in parallel with a further decline in Vmax to 51 +/- 25 V/s (P < .05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na+ channel availability curves generated from both theta 2 and Vmax, used as indexes of the fast inward INa, without changing the slopes of the relation. The relation between normalized theta 2 and Vmax over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
Munger
T M
TM
Department of Internal Medicine, Mayo Foundation, Rochester, Minn. 55905.
Johnson
S B
SB
Packer
D L
DL
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004285:Dogs; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D015737:Nisoldipine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; D015737:Nisoldipine; D007545:Isoproterenol