Distinct properties of the atrial voltage-gated sodium channel

O'Brien, Sian-Marie (2019). Distinct properties of the atrial voltage-gated sodium channel. University of Birmingham. Ph.D.

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Abstract

Sodium handling properties of left atria (LA) were compared to those of left ventricle (LV), with the aim to understand the atria’s susceptibility to arrhythmia and improve therapy. Mouse LA sodium channels displayed distinctive activation, inactivation and recovery kinetics compared to LV sodium channels. Distinctive voltage dependence of LA sodium channel inactivation was instrumental in reducing INa in LA compared to LV, when initiated from physiological holding potentials. Flecainide sodium channel inhibition was greater in LA than LV, likely also due to differences in kinetic properties of the sodium channels between chambers. Additionally, the greater inhibitory effect of flecainide at more positive membrane potentials could result in even greater LA sodium channel inhibition in vivo.

Activation and inactivation distinctions observed between LA and LV sodium channels were conserved between chambers in the Plako+/- mouse. However, there was no difference in physiological INa density, sodium channel recovery or flecainide inhibition between Plako+/- LA and LV chambers.

The novel Langendorff-free isolation method produced high yields of viable mouse cardiomyocytes comparable in morphology, signalling, calcium handling and sodium channel electrophysiology to cardiomyocytes isolated using the traditional Langendorff method. This maintained that injection isolation is a valuable method for obtaining cardiomyocytes for cardiac research.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):