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Ca-dependent outward currents in bullfrog myocardium
Abstract:
Properties of Ca-dependent outward current were studied in bullfrog atrial muscle using double sucrose-gap techniques. Decreasing [Ca]o inhibited the instantaneous outward current (Ik1) and inward background current (Ib), and the reverse was noted with increases in [Ca]o. When gk1 was blocked with 0.3 mM Ba, there were no such effects. In the presence of Ba and TTX (1.5 X 10(-6)M), 3 mM Co abolished the slow inward current (Isi) and depressed the delayed outward current (Iout). The depression was confined to the voltage range of activation of Isi. Similar results were obtained by replacement of [Ca]o with Co in concentration of equal surface charge effects. Contrarily, isoproterenol (10(-7) M) increased the Isi and Iout at the same voltage range. The activation of Iout became more rapid in the presence of isoproterenol but slowed with Co. In the presence of Ba, TTX, and Co, Ca-free EGTA (approximately 0.3 mM) Ringer further depressed the Iout, eliminating any remaining tension response. The depression, however, was more extensive, the stronger the depolarization. The activation of Iout was markedly retarded and amplitude of the fully activated Iout diminished, yet the deactivation became more rapid. Thus, the Ca-sensitive outward current was classified into 1) Ca-linked Ik1, 2) Isi-dependent Iout, and 3) Isi-independent but [Ca]o-related Iout.
Insights
Calcium ions significantly influence outward currents in bullfrog atrial muscle. Researchers identified three distinct calcium-sensitive outward currents, impacting cardiac electrical activity and muscle contraction.
Area of Science:
- Cardiac Electrophysiology
- Ion Channel Physiology
- Cardiovascular Pharmacology
Background:
- Calcium ions (Ca2+) play a crucial role in cardiac muscle function, regulating both excitation-contraction coupling and electrical activity.
- Outward currents are essential for cardiac repolarization and maintaining the cardiac action potential.
- Understanding the specific properties and regulation of Ca2+-dependent currents is vital for comprehending cardiac electrophysiology.
Purpose of the Study:
- To investigate the properties of Ca2+-dependent outward currents in bullfrog atrial muscle.
- To elucidate the relationship between extracellular calcium concentration ([Ca]o) and specific ionic currents.
- To classify the different components of Ca2+-sensitive outward currents.
Main Methods:
- Utilized double sucrose-gap techniques to study ionic currents in bullfrog atrial muscle.
- Manipulated extracellular calcium concentrations ([Ca]o) and employed specific blockers (Ba2+, TTX, Co2+, EGTA) to isolate and characterize currents.
- Investigated the effects of isoproterenol on ionic currents.
Main Results:
- Decreasing [Ca]o inhibited instantaneous outward current (Ik1) and inward background current (Ib); increasing [Ca]o had the opposite effect.
- Barium (Ba2+) blocked Ik1, indicating these effects were Ca2+-dependent.
- Cobalt (Co2+) abolished slow inward current (Isi) and depressed delayed outward current (Iout) in a voltage-dependent manner, while isoproterenol enhanced both currents.
- Ca2+-free conditions further depressed Iout, altering activation and deactivation kinetics.
Conclusions:
- Identified and classified three distinct Ca2+-sensitive outward currents: Ca2+-linked Ik1, Isi-dependent Iout, and Isi-independent but [Ca]o-related Iout.
- Demonstrated the significant role of extracellular calcium in modulating cardiac outward currents and their kinetics.
- Highlighted the differential effects of pharmacological agents (Co2+, isoproterenol) on these currents, providing insights into cardiac electrophysiological regulation.