Open AccessMechanism of Block by 4-Aminopyridine of the Transient Outward Current in Rat Ventricular Cardiomyocytes
Author(s) -
Jörg W. Wegener,
Angela Peiter,
Sanford R. Sampson,
Hermann Nawrath
Publication year - 1998
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199807000-00021
Subject(s) - intracellular , biophysics , extracellular , protonation , chemistry , 4 aminopyridine , cardiac transient outward potassium current , amine gas treating , membrane potential , intracellular ph , block (permutation group theory) , membrane , biochemistry , patch clamp , ion , potassium channel , biology , receptor , geometry , mathematics , organic chemistry
The effects of 4-aminopyridine (4-AP) on the transient outward current (I(to)) were investigated in rat ventricular cardiomyocytes at different values of intracellular pH (pHi) and extracellular pH (pHo). The 4-AP was administered either extracellularly (bath application) or intracellularly (diffusion from the intrapipette solution). The 4-AP diminished I(to) given either from inside or outside the cell membrane. The block by extracellularly applied 4-AP (4-APo) of the peak amplitude of I(to) was decreased by external acidification but increased by external alkalinization; conversely, the block by 4-APo was decreased by internal alkalinization but increased by internal acidification. Intracellularly applied 4-AP (3 mM) was more effective at low pHi. Because 4-AP is a tertiary amine and exists in protonated and unprotonated forms, these results are in agreement with the assumption that one major mechanism for 4-AP to block I(to) is to penetrate the cell membrane in its uncharged form and to reach intracellular binding sites in its protonated form.