期刊
PHYSIOLOGICAL REPORTS
卷 7, 期 1, 页码 -出版社
WILEY
DOI: 10.14814/phy2.13862
关键词
Biological pacemaker; conduction; ionic theory; patch
类别
Initially, diastolic depolarization in Purkinje fibers was explained by deactivation of gK2 in the presence of inward current. Weakness of the hypothesis was a too negative reversal potential, sensitivity to external Na+ ions, existence of K+ depletion, and fake current during hyperpolarizing clamps. The development of a sinus node preparation of almost microscopic dimensions allowing uniform voltage clamps created new possibilities. Three different groups discovered in this improved node preparation an hyperpolarization induced time-dependent inward current, with a reversal potential positive to the resting potential, carried by a mixture of Na+ and K+ ions. A new current, If, or funny current was born. It is not the only pacemaker current. The following sequence of currents (membrane clock) has been proposed: diastole starts as a consequence of IK deactivation and If activation; followed by activation of the T-type Ca2+ current, Ca2+-induced Ca2+ release from the SR, and activation of sodium-calcium exchange current with further depolarization of the membrane till threshold of the L-type Ca(2+)current is reached. The release of Ca2+ can also occur spontaneously independently from a T-type Ca(2+)current. The system acts then as a primary intracellular clock. The review is completed by description of an evolution in the direction of biological pacing using induced pluripotent stem cells or transcription factors.
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