Regional differences in effects of 4-aminopyridine within the sinoatrial node.
4-Aminopyridine (4-AP)-sensitive transient outward current (Ito) has been observed in the sinoatrial node, but its role is unknown. The effect of block of Ito by 5 mM 4-AP on small ball-like tissue preparations (diameter approximately 0.3-0.4 mm) from different regions of the rabbit sinoatrial node has been investigated. 4-AP elevated the plateau, prolonged the action potential, and decreased the maximum diastolic potential. Effects were greater in tissue from the periphery of the node than from the center. In peripheral tissue, 4-AP abolished the action potential notch, if present. 4-AP slowed pacemaker activity of peripheral tissue but accelerated that of central tissue. Differences in the response to 4-AP were also observed between tissue from more superior and inferior regions of the node. In the intact sinoatrial node, 4-AP resulted in a shift of the leading pacemaker site consistent with the regional differences in the response to 4-AP. It is concluded that 4-AP-sensitive outward current plays a major role in action potential repolarization and pacemaker activity in the sinoatrial node and that its role varies regionally.
Boyett
M R
MR
Department of Physiology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Honjo
H
H
Yamamoto
M
M
Nikmaram
M R
MR
Niwa
R
R
Kodama
I
I
D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D011817:Rabbits; D012044:Regression Analysis; D012849:Sinoatrial Node / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D015761:4-Aminopyridine