title: Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.
abstract: The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35-37°C. Hyperpolarizing voltage commands from -40 mV elicited a Ba(2+)-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from -40 mV L-type Ca(2+) current, IC a,L, was elicited with a half maximal activation voltage (V0.5) of -7.6 ± 1.2 mV (n = 24). IC a,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IK r) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to -40 mV, with an activation V0.5 of -10.7 ± 4.7 mV (n = 8). The IK r magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (-40 mV). Spontaneous APs (5.2 ± 0.5 sec(-1); n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca(2+) release by 1 μmol/L ryanodine, implicating intracellular Ca(2+) cycling in murine AVN cell electrogenesis.
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.
authors.forename: Stéphanie C
authors.initials: SC
authors.lastname: Choisy
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cheng
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.
authors.forename: Clive H
authors.initials: CH
authors.lastname: Orchard
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: James
authors.affiliation: School of Physiology and Pharmacology and Cardiovascular Research Laboratories, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom jules.hancox@bristol.ac.uk.
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
keywords: AV node; AVN; I
  C
  
  a,L; I
  K
  
  r; I
  NCX; I
  f; atrioventricular node; calcium‐current; hyperpolarization‐activated current; pacemaking; rapid delayed rectifier; ryanodine