HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rasmusson, R L Articles by Strauss, H C Search for Related Content PubMed PubMed Citation Articles by Rasmusson, R L Articles by Strauss, H C

Department of Biomedical Engineering, Duke University Durham, NC 27710, USA.

1. Using the two-microelectrode, 'cut open' oocyte, and 'torn off' macropatch voltage clamp techniques, we studied the blocking effects of 4-aminopyridine (4-AP) on two cloned K+ channels expressed in Xenopus oocytes, an inactivating K+ channel isolated from ferret ventricle (FK1), and its NH2-terminal deletion mutant (delta NCO) which lacks fast N-type inactivation. 2. Experiments with a permanently charged, impermeant 4-AP derivative, 4-aminopyridine-methyliodide, indicated that the cationic form of 4-AP blocks at an intracellular site. 3. Block accumulated from pulse to pulse and was sensitive to the applied potential during hyperpolarizing deactivating pulses, indicating trapping of 4-AP in deactivated channels. For long trains of depolarizing pulses (-90 to +50 mV, 0.1 Hz), 4-AP block increased with decreasing pulse duration. Block of FK1 was much more sensitive to pulse duration than was block of delta NCO, consistent with competition between N-type inactivation and 4-AP binding. 4. To elucidate these mechanisms further, in the absence of fast N-type inactivation the following results were obtained on delta NCO channels: (1) application of 4-AP caused the appearance of apparent inactivation; (2) 4-AP, however, did not cause cross-over of deactivating tail currents; (3) 4-AP block developed with time for potentials positive to -40 mV; and (4) trapping of 4-AP by delta NCO was insensitive to the degree of C-type inactivation. 5. We conclude that the kinetics of 4-AP block of FK1 and delta NCO channels cannot be accounted for by either a pure open channel or closed channel blocking scheme.

This article has been cited by other articles:

				H.-L. Li, Y.-J. Qu, Y. C. Lu, V. E. Bondarenko, S. Wang, I. M. Skerrett, and M. J. Morales DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4 Am J Physiol Cell Physiol, November 1, 2006; 291(5): C966 - C976. [Abstract] [Full Text] [PDF]

				S. P. Patel and D. L. Campbell Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms J. Physiol., November 15, 2005; 569(1): 7 - 39. [Abstract] [Full Text] [PDF]

				G.-N. Tseng Different State Dependencies of 4-Aminopyridine Binding to rKv1.4 and rKv4.2: Role of the Cytoplasmic Halves of the Fifth and Sixth Transmembrane Segments J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 569 - 577. [Abstract] [Full Text]

				R. L. Rasmusson, M. J. Morales, S. Wang, S. Liu, D. L. Campbell, M. V. Brahmajothi, and H. C. Strauss Inactivation of Voltage-Gated Cardiac K+ Channels Circ. Res., April 20, 1998; 82(7): 739 - 750. [Abstract] [Full Text] [PDF]

				S. Liu, R. B. Melchert, and R. H. Kennedy Inhibition of L-Type Ca2+ Channel Current in Rat Ventricular Myocytes by Terfenadine Circ. Res., August 19, 1997; 81(2): 202 - 210. [Abstract] [Full Text]