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A quaternary derivative of diltiazem (quat-DTZ) was tested to determine whether diltiazem approaches L-type Ca2+ channels from the outside or inside of the cell membrane. In single ventricular myocytes, both extra- and intracellular application of quat-DTZ effectively blocked the L-type Ca2+ channel current, whereas D890 was effective only when applied intracellularly. These results strongly suggest that diltiazem binds to the channel from the outside as well as the inside of the membrane in a manner different from that of phenylalkylamines.

Quaternary Diltiazem Can Act from Both Sides of the Membrane in Ventricular Myocytes