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Abstract
Activation of voltage-gated sodium channels (VGSC) underlies the generation and propagation of cardiac action potentials while their subsequent inactivation establishes a refractory period. Blockers of VGSC are highly effective as antiarrhythmic drugs in the treatment of atrial fibrillation. However, their use is limited because ventricular arrhythmias are a common side-effect. Atrial-ventricular differences in VGSC might be exploited to develop atrial-selective antiarrhythmic action. In this study, atrial-ventricular differences in the steady-state voltagedependent activation and inactivation of fast VGSC currents (INa)
were examined. INa was recorded from rat left atrial (n= 11) and left ventricular myocytes (n= 11) at room temperature using the whole-cell patch clamp technique. Recording solutions contained low equimolar sodium (5 mM) and Co2þ (1 mM) was used to block calcium currents. Voltage protocols had a holding potential of 120 mV. INa was recorded in response to a range of test pulses to investigate activation and at 30 mV following a range of conditioning pulses to investigate steadystateinactivation. Currents were normalized to whole-cell capacitance as an index of cell size and mean current-density voltage relations fitted by a modified Boltzmann relation. There was no significant difference between atrial and ventricular cells in current density-voltage relations: half-maximal voltages (V1/2) of activation were atrial, 47.851.5 mV, and ventricular, 46.851.1 mV. On the other hand, the V1/2 of inactivation for atrial and ventricular myocytes were 93.45 +/- 0.5 mV and 87.45 +/- 0.3 mV, respectively. Therefore, INa inactivation occurred at more negative voltages in rat atrial myocytes compared to ventricular myocytes.
were examined. INa was recorded from rat left atrial (n= 11) and left ventricular myocytes (n= 11) at room temperature using the whole-cell patch clamp technique. Recording solutions contained low equimolar sodium (5 mM) and Co2þ (1 mM) was used to block calcium currents. Voltage protocols had a holding potential of 120 mV. INa was recorded in response to a range of test pulses to investigate activation and at 30 mV following a range of conditioning pulses to investigate steadystateinactivation. Currents were normalized to whole-cell capacitance as an index of cell size and mean current-density voltage relations fitted by a modified Boltzmann relation. There was no significant difference between atrial and ventricular cells in current density-voltage relations: half-maximal voltages (V1/2) of activation were atrial, 47.851.5 mV, and ventricular, 46.851.1 mV. On the other hand, the V1/2 of inactivation for atrial and ventricular myocytes were 93.45 +/- 0.5 mV and 87.45 +/- 0.3 mV, respectively. Therefore, INa inactivation occurred at more negative voltages in rat atrial myocytes compared to ventricular myocytes.
Original language | English |
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Pages | 626a |
Number of pages | 1 |
DOIs | |
Publication status | Published - 2 Feb 2018 |
Event | 62nd Annual Meeting of the Biophysical Society - Moscone Convention Center, San Francisco, United States Duration: 17 Feb 2018 → 21 Feb 2018 Conference number: 62 https://www.biophysics.org/2018meeting/Home/tabid/7117/Default.aspx |
Conference
Conference | 62nd Annual Meeting of the Biophysical Society |
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Abbreviated title | Biophysics 2018 |
Country/Territory | United States |
City | San Francisco |
Period | 17/02/18 → 21/02/18 |
Internet address |
Keywords
- voltage-gated sodium current
- Cardiac myocytes
- atrial-selective
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Dive into the research topics of 'Fast Sodium Currents in Rat Atrial and Ventricular Myocytes'. Together they form a unique fingerprint.Projects
- 1 Finished
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Selective late sodium current blockers as antiarrhythmic drugs in atrial fibrillation
James, A. F. (Principal Investigator)
14/03/16 → 13/03/19
Project: Research