Does the small conductance Ca2+-activated K+ current ISK flow under physiological conditions in rabbit and human atrial isolated cardiomyocytes?
J Mol Cell Cardiol
; 183: 70-80, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37704101
ABSTRACT
BACKGROUND:
The small conductance Ca2+-activated K+ current (ISK) is a potential therapeutic target for treating atrial fibrillation.AIM:
To clarify, in rabbit and human atrial cardiomyocytes, the intracellular [Ca2+]-sensitivity of ISK, and its contribution to action potential (AP) repolarisation, under physiological conditions.METHODS:
Whole-cell-patch clamp, fluorescence microscopy to record ion currents, APs and [Ca2+]i; 35-37°C.RESULTS:
In rabbit atrial myocytes, 0.5 mM Ba2+ (positive control) significantly decreased whole-cell current, from -12.8 to -4.9 pA/pF (P < 0.05, n = 17 cells, 8 rabbits). By contrast, the ISK blocker apamin (100 nM) had no effect on whole-cell current, at any set [Ca2+]i (â¼100-450 nM). The ISK blocker ICAGEN (1 µM ≥2 x IC50) also had no effect on current over this [Ca2+]i range. In human atrial myocytes, neither 1 µM ICAGEN (at [Ca2+]i â¼ 100-450 nM), nor 100 nM apamin ([Ca2+]i â¼ 250 nM) affected whole-cell current (5-10 cells, 3-5 patients/group). APs were significantly prolonged (at APD30 and APD70) by 2 mM 4-aminopyridine (positive control) in rabbit atrial myocytes, but 1 µM ICAGEN had no effect on APDs, versus either pre-ICAGEN or time-matched controls. High concentration (10 µM) ICAGEN (potentially ISK-non-selective) moderately increased APD70 and APD90, by 5 and 26 ms, respectively. In human atrial myocytes, 1 µM ICAGEN had no effect on APD30-90, whether stimulated at 1, 2 or 3 Hz (6-9 cells, 2-4 patients/rate).CONCLUSION:
ISK does not flow in human or rabbit atrial cardiomyocytes with [Ca2+]i set within the global average diastolic-systolic range, nor during APs stimulated at physiological or supra-physiological (≤3 Hz) rates.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Miócitos Cardíacos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article