Mechanisms of quinidine-induced depression of maximum upstroke velocity in ovine cardiac Purkinje fibers

F. M. Weld, J. Coromilas, J. N. Rottman, J. T. Bigger

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

A major advance in understanding how quinidine depresses maximum upstroke velocity (V̇(max)) is the Hondeghem-Katzung mathematical model which incorporates voltage-independent rate constants for binding to and unbinding from resting, open, and inactive Na channels, and a voltage shift of -40 mV for the Hodgkin-Huxley h-kinetics of quinidine-associated Na channels. Using a double microelectrode voltage clamp technique to control transmembrane voltage and apply conditioning pulses, we found that quinidine blockade increased as transmembrane voltage became more positive in the range -60 to +40 mV, and that the rate of quinidine dissociation increased as transmembrane voltage became more negative in the range -60 to -140 mV. The relationship of V̇(max) to transmembrane voltage obtained at drive cycles from 500 msec to 20 seconds conformed to the model modified to include voltage-dependent rate constants without the postulated -40-mV shift for quinidine-associated channels. Thus binding of quinidine to inactive Na channels and unbinding from resting channels are both voltage-dependent and can explain frequency and voltage dependent actions of quinidine on V̇(max) without any voltage shift for quinidine-associated channels.

Original languageEnglish (US)
Pages (from-to)369-376
Number of pages8
JournalCirculation research
Volume50
Issue number3
DOIs
StatePublished - 1982
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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