Abstract
1. 1. Single myocytes were isolated from the rabbit atrioventricular node (AVN) and whole cell patch clamped, using a Cs +-based internal dialysis solution. Depolarizing voltage clamps from a holding potential of −40 mV were applied to investigate the effects of the antiarrhythmic agent amiodarone on L-type calcium current (I Ca,L). 2. 2. The current-voltage (I–V) relation for I Ca,L was bell shaped in normal Tyrode's solution, with a peak at +10 mV. After a 1-min exposure to 10 μM amiodarone, I Ca,L at all potentials between −30 mV and +60 mV was largely and reversibly blocked ( n=4). In 13 cells, peak I Ca,L was blocked by 85% after amiodarone application. 3. 3. The time course of the blocking effect was monitored during continuous pulsing (at 0.33 Hz) from −40 mV to + 10 mV to observe the time course of I Ca,L blockade. This could be described by a single exponential function with a rate constant of 0.21 per second. In other cells, amiodarone was applied for 30 sec without any stimulation; and, when stimulation was resumed, the I Ca,L amplitude with the first pulse was 22% of the control amplitude ( n=4), indicating that a substantial portion of the blockade of I Ca,L by amiodarone was tonic in nature. 4. 4. In addition to the effect of amiodarone on the I Ca,L channel, when the β adrenergic agonist isoprenaline (1 μM) was applied to cells that had been pretreated with amiodarone, I Ca,L amplitude was increased by 44.5±10.8% ( n=4). In cells that had received no such pretreatment with amiodarone, isoprenaline increased the I Ca,L amplitude by 101.5±5.9% ( n=4). Thus, isoprenaline produced a larger increase in I Ca,L in the absence of amiodarone than in its presence ( P<0.001). 5. 5. It is concluded that, in single AVN cells, amiodarone exerts a direct I Ca,L blocking action. In addition, the attenuated increase in I Ca,L with isoprenaline in amiodarone pretreated cells appears consistent with an antagonism of β adrenergic stimulation of I Ca,L.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.