Pacemaker activity and ionic currents in mouse atrioventricular node cells.
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Pacemaker activity and ionic currents in mouse atrioventricular node cells. / Marger, Laurine; Mesirca, Pietro; Alig, Jacqueline; Torrente, Angelo; Dubel, Stefan; Engeland, Birgit; Kanani, Sandra; Fontanaud, Pierre; Striessnig, Jörg; Shin, Hee-Sup; Isbrandt, Dirk; Ehmke, Heimo; Nargeot, Joël; Mangoni, Matteo E.
In: CHANNELS, Vol. 5, No. 3, 3, 2011, p. 241-250.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pacemaker activity and ionic currents in mouse atrioventricular node cells.
AU - Marger, Laurine
AU - Mesirca, Pietro
AU - Alig, Jacqueline
AU - Torrente, Angelo
AU - Dubel, Stefan
AU - Engeland, Birgit
AU - Kanani, Sandra
AU - Fontanaud, Pierre
AU - Striessnig, Jörg
AU - Shin, Hee-Sup
AU - Isbrandt, Dirk
AU - Ehmke, Heimo
AU - Nargeot, Joël
AU - Mangoni, Matteo E
PY - 2011
Y1 - 2011
N2 - It is well established that Pacemaker activity of the sino-atrial node (SAN) initiates the heartbeat. However, the atrioventricular node (AVN) can generate viable pacemaker activity in case of SAN failure, but we have limited knowledge of the ionic bases of AVN automaticity. We characterized pacemaker activity and ionic currents in automatic myocytes of the mouse AVN. Pacemaking of AVN cells (AVNCs) was lower than that of SAN pacemaker cells (SANCs), both in control conditions and upon perfusion of isoproterenol (ISO). Block of I(Na) by tetrodotoxin (TTX) or of I(Ca,L) by isradipine abolished AVNCs pacemaker activity. TTX-resistant (I(Nar)) and TTX-sensitive (I(Nas)) Na(+) currents were recorded in mouse AVNCs, as well as T-(I(Ca,T)) and L-type (I(Ca,L)) Ca(2+) currents I(Ca,L) density was lower than in SANCs (51%). The density of the hyperpolarization-activated current, (I(f)) and that of the fast component of the delayed rectifier current (I(Kr)) were, respectively, lower (52%) and higher (53%) in AVNCs than in SANCs. Pharmacological inhibition of I(f) by 3 µM ZD-7228 reduced pacemaker activity by 16%, suggesting a relevant role for I(f) in AVNCs automaticity. Some AVNCs expressed also moderate densities of the transient outward K(+) current (I(to)). In contrast, no detectable slow component of the delayed rectifier current (I(Ks)) could be recorded in AVNCs. The lower densities of I(f) and I(Ca,L), as well as higher expression of I(Kr) in AVNCs than in SANCs may contribute to the intrinsically slower AVNCs pacemaking than that of SANCs.
AB - It is well established that Pacemaker activity of the sino-atrial node (SAN) initiates the heartbeat. However, the atrioventricular node (AVN) can generate viable pacemaker activity in case of SAN failure, but we have limited knowledge of the ionic bases of AVN automaticity. We characterized pacemaker activity and ionic currents in automatic myocytes of the mouse AVN. Pacemaking of AVN cells (AVNCs) was lower than that of SAN pacemaker cells (SANCs), both in control conditions and upon perfusion of isoproterenol (ISO). Block of I(Na) by tetrodotoxin (TTX) or of I(Ca,L) by isradipine abolished AVNCs pacemaker activity. TTX-resistant (I(Nar)) and TTX-sensitive (I(Nas)) Na(+) currents were recorded in mouse AVNCs, as well as T-(I(Ca,T)) and L-type (I(Ca,L)) Ca(2+) currents I(Ca,L) density was lower than in SANCs (51%). The density of the hyperpolarization-activated current, (I(f)) and that of the fast component of the delayed rectifier current (I(Kr)) were, respectively, lower (52%) and higher (53%) in AVNCs than in SANCs. Pharmacological inhibition of I(f) by 3 µM ZD-7228 reduced pacemaker activity by 16%, suggesting a relevant role for I(f) in AVNCs automaticity. Some AVNCs expressed also moderate densities of the transient outward K(+) current (I(to)). In contrast, no detectable slow component of the delayed rectifier current (I(Ks)) could be recorded in AVNCs. The lower densities of I(f) and I(Ca,L), as well as higher expression of I(Kr) in AVNCs than in SANCs may contribute to the intrinsically slower AVNCs pacemaking than that of SANCs.
KW - Animals
KW - Mice
KW - Mice, Transgenic
KW - Biological Clocks/drug effects/physiology
KW - Pyrimidines/pharmacology
KW - Atrioventricular Node/cytology/metabolism
KW - Calcium Channel Blockers/pharmacology
KW - Cardiovascular Agents/pharmacology
KW - Drug Resistance/drug effects/physiology
KW - Ion Transport/drug effects/physiology
KW - Isradipine/pharmacology
KW - Membrane Potentials/drug effects/physiology
KW - Myocardial Contraction/drug effects/physiology
KW - Myocytes, Cardiac/cytology/metabolism
KW - Potassium Channels, Tandem Pore Domain/antagonists & inhibitors/genetics/metabolism
KW - Sinoatrial Node/cytology/metabolism
KW - Sodium Channel Blockers/pharmacology
KW - Tetrodotoxin/pharmacology
KW - Animals
KW - Mice
KW - Mice, Transgenic
KW - Biological Clocks/drug effects/physiology
KW - Pyrimidines/pharmacology
KW - Atrioventricular Node/cytology/metabolism
KW - Calcium Channel Blockers/pharmacology
KW - Cardiovascular Agents/pharmacology
KW - Drug Resistance/drug effects/physiology
KW - Ion Transport/drug effects/physiology
KW - Isradipine/pharmacology
KW - Membrane Potentials/drug effects/physiology
KW - Myocardial Contraction/drug effects/physiology
KW - Myocytes, Cardiac/cytology/metabolism
KW - Potassium Channels, Tandem Pore Domain/antagonists & inhibitors/genetics/metabolism
KW - Sinoatrial Node/cytology/metabolism
KW - Sodium Channel Blockers/pharmacology
KW - Tetrodotoxin/pharmacology
U2 - 10.4161/chan.5.3.15264
DO - 10.4161/chan.5.3.15264
M3 - SCORING: Journal article
VL - 5
SP - 241
EP - 250
JO - CHANNELS
JF - CHANNELS
SN - 1933-6950
IS - 3
M1 - 3
ER -
