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Ionic basis of ryanodine's negative chronotropic effect on pacemaker cells isolated from the sinoatrial node
J Li1, J Qu, R D Nathan
1Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
The American Journal of Physiology
|December 31, 1997
Summary
Ryanodine and BAPTA-AM reduce intracellular calcium transients and slow heart rate in pacemaker cells. This suggests T-type calcium channel current reduction contributes to ryanodine
Area of Science:
- Cardiovascular Physiology
- Cell Biology
- Pharmacology
Background:
- Sinoatrial node pacemaker cells exhibit spontaneous electrical activity crucial for heart rhythm.
- Intracellular calcium (Ca2+) transients play a pivotal role in regulating cardiac pacemaker cell function.
- The precise mechanisms by which calcium handling influences spontaneous electrical activity are under investigation.
Purpose of the Study:
- To investigate the role of intracellular calcium handling in regulating spontaneous electrical activity in rabbit sinoatrial node pacemaker cells.
- To elucidate the effects of ryanodine and BAPTA-AM on calcium transients and electrical activity.
- To determine the contribution of specific calcium currents and Na/Ca exchange to the observed effects.
Main Methods:
- Simultaneous recording of spontaneous electrical activity and indo-1 fluorescence ratios in cultured rabbit sinoatrial node pacemaker cells.
- Application of ryanodine (10 microM) and 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (AM; 25 microM).
- Measurement of hyperpolarization-activated current, time-independent inward current, L-type and T-type calcium currents (ICa,L and ICa,T), and Na/Ca exchange current (INa/Ca).
Main Results:
- Ryanodine reduced action potential-induced Ca2+i transient amplitude by 19% and slowed decay by 51%, slowing spontaneous firing by 32%.
- BAPTA-AM inhibited Ca2+i transients and slowed spontaneous firing by 28%.
- Ryanodine reduced ICa,L and ICa,T currents, while BAPTA or ryanodine abolished INa/Ca.
- ICa,L remained unchanged by ryanodine.
Conclusions:
- A decrease in T-type calcium current (ICa,T), potentially due to reduced intracellular calcium or direct ryanodine effects, contributes to the negative chronotropic effect.
- Reduced Na/Ca exchange current (INa/Ca) secondary to smaller Ca2+i transients may also contribute to ryanodine's chronotropic effect.
- These findings highlight the complex interplay between calcium handling and electrical activity in sinoatrial node pacemaker cells.