Properties of the pacemaker current (I(f)) in latent pacemaker cells isolated from cat right atrium

Zhengfeng Zhou, S. L. Lipsius

Research output: Contribution to journalArticle

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Abstract

1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 ± 1 to -54 ± 2 mV and its cycle length was 901 ± 67 ms (72 ± 5 beats min-1) at 34-36° C. Cells were elongated with tapered ends and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 ± 0.5 μm and 93.1 ± 5.9 μm, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 ± 0.2 GΩ and 27.8 ± 3.1 pF respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a timedependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4 respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 ± 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 ± 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2mM) inhibited I(f) by more than 90% (at -70 mV), and decreased the slope of diastolic depolarization resulting in a 48 ± 5% decrease in spontaneous rate. 7. The present experiments demonstrate the isolation of Ca2+-tolerant latent pacemaker cells from the Eustachian ridge of cat right atrium. Latent atrial pacemakers appear morphologically and clectrophysiologically similar, though not identical, to pacemaker cells isolated from sino-atrial (SA) node. The hyperpolarization-activated inward current, I(f) is activated within the latent pacemaker voltage range and contributes significantly to latent pacemaker function. The relatively long time course and small amplitude of I(f) activation may explain, in part, the relatively long spontaneous cycle length of latent atrial pacemakers.

Original languageEnglish (US)
Pages (from-to)503-523
Number of pages21
JournalJournal of Physiology
Volume453
StatePublished - 1992
Externally publishedYes

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Heart Atria
Cats
Cesium
Nystatin
Sinoatrial Node
Patch-Clamp Techniques
Action Potentials
Perfusion
Membranes
Enzymes

ASJC Scopus subject areas

  • Physiology

Cite this

Properties of the pacemaker current (I(f)) in latent pacemaker cells isolated from cat right atrium. / Zhou, Zhengfeng; Lipsius, S. L.

In: Journal of Physiology, Vol. 453, 1992, p. 503-523.

Research output: Contribution to journalArticle

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title = "Properties of the pacemaker current (I(f)) in latent pacemaker cells isolated from cat right atrium",
abstract = "1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 ± 1 to -54 ± 2 mV and its cycle length was 901 ± 67 ms (72 ± 5 beats min-1) at 34-36° C. Cells were elongated with tapered ends and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 ± 0.5 μm and 93.1 ± 5.9 μm, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 ± 0.2 GΩ and 27.8 ± 3.1 pF respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a timedependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4 respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 ± 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 ± 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2mM) inhibited I(f) by more than 90{\%} (at -70 mV), and decreased the slope of diastolic depolarization resulting in a 48 ± 5{\%} decrease in spontaneous rate. 7. The present experiments demonstrate the isolation of Ca2+-tolerant latent pacemaker cells from the Eustachian ridge of cat right atrium. Latent atrial pacemakers appear morphologically and clectrophysiologically similar, though not identical, to pacemaker cells isolated from sino-atrial (SA) node. The hyperpolarization-activated inward current, I(f) is activated within the latent pacemaker voltage range and contributes significantly to latent pacemaker function. The relatively long time course and small amplitude of I(f) activation may explain, in part, the relatively long spontaneous cycle length of latent atrial pacemakers.",
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N2 - 1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 ± 1 to -54 ± 2 mV and its cycle length was 901 ± 67 ms (72 ± 5 beats min-1) at 34-36° C. Cells were elongated with tapered ends and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 ± 0.5 μm and 93.1 ± 5.9 μm, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 ± 0.2 GΩ and 27.8 ± 3.1 pF respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a timedependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4 respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 ± 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 ± 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2mM) inhibited I(f) by more than 90% (at -70 mV), and decreased the slope of diastolic depolarization resulting in a 48 ± 5% decrease in spontaneous rate. 7. The present experiments demonstrate the isolation of Ca2+-tolerant latent pacemaker cells from the Eustachian ridge of cat right atrium. Latent atrial pacemakers appear morphologically and clectrophysiologically similar, though not identical, to pacemaker cells isolated from sino-atrial (SA) node. The hyperpolarization-activated inward current, I(f) is activated within the latent pacemaker voltage range and contributes significantly to latent pacemaker function. The relatively long time course and small amplitude of I(f) activation may explain, in part, the relatively long spontaneous cycle length of latent atrial pacemakers.

AB - 1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 ± 1 to -54 ± 2 mV and its cycle length was 901 ± 67 ms (72 ± 5 beats min-1) at 34-36° C. Cells were elongated with tapered ends and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 ± 0.5 μm and 93.1 ± 5.9 μm, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 ± 0.2 GΩ and 27.8 ± 3.1 pF respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a timedependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4 respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 ± 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 ± 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2mM) inhibited I(f) by more than 90% (at -70 mV), and decreased the slope of diastolic depolarization resulting in a 48 ± 5% decrease in spontaneous rate. 7. The present experiments demonstrate the isolation of Ca2+-tolerant latent pacemaker cells from the Eustachian ridge of cat right atrium. Latent atrial pacemakers appear morphologically and clectrophysiologically similar, though not identical, to pacemaker cells isolated from sino-atrial (SA) node. The hyperpolarization-activated inward current, I(f) is activated within the latent pacemaker voltage range and contributes significantly to latent pacemaker function. The relatively long time course and small amplitude of I(f) activation may explain, in part, the relatively long spontaneous cycle length of latent atrial pacemakers.

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