The FASEB Journal, Vol 10, 357-361, Copyright © 1996 by The Federation of American Societies for Experimental Biology

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Cytoskeletal control of rectification and expression of four substates in cardiac inward rectifier K+ channels

M Mazzanti, R Assandri, A Ferroni and D DiFrancesco
Dipartimento di Fisiologia e Biochimica Generali, Universita di Milano, Italy.

Cardiac inward rectifiers may have a three-barrel channel structure, based on evidence for three substates in single-channel recordings. However, some reports indicate four substates, a feature more compatible with the four-subunit structure for which there is evidence in cloned voltage-activated K+ channels. Here we show that although the fourth is easily missed, inward rectifier channels have four substates whose expression is controlled by intracellular Ca(2+) ions. Fourth substate openings also appear after rectification loss in intracellular divalent caution-free solution. We find that this process is accelerated by cytochalasin, a microfilament disrupter. Cytochalasin also abolishes Ca(2+), but not Mg(2+),-induced rectification by restoring fourth substate openings. Thus, cytoskeletal elements control Ca(2+)-dependent substate expression and rectification in native inwardly rectifying K+ channels.

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