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- Title
Stretch-activated and background non-selective cation channels in rat atrial myocytes.
- Authors
Zhang, Yin Hua; Youm, Jae Boum; Sung, Ho Kyung; Lee, Sang Hyun; Ryu, Shin Young; Lee, Suk-Ho; Ho, Won-Kyung; Earm, Yung E.
- Abstract
Stretch-activated channels (SACs) were studied in isolated rat atrial myocytes using the whole-cell and single-channel patch clamp techniques. Longitudinal stretch was applied by using two patch electrodes., In current clamp configuration, mechanical stretch of 20 % of resting cell length depolarised the resting membrane potential (RMP) from -63·6 ± 0·58 mV ( n= 19) to -54·6 ± 2·4 mV ( n= 13) and prolonged the action potential duration (APD) by 32·2 ± 8·8 ms ( n= 7). Depolarisation, if strong enough, triggered spontaneous APs. In the voltage clamp configuration, stretch increased membrane conductance in a progressive manner. The current-voltage ( I-V) relationship of the stretch-activated current (ISAC) was linear and reversed at -6·1 ± 3·7 mV ( n= 7)., The inward component of ISAC was abolished by the replacement of Na+ with NMDG+, but ISAC was hardly altered by the Cl− channel blocker DIDS or removal of external Cl−. The permeability ratio for various cations ( PCs: PNa: PLi= 1·05:1:0·98) indicated that the SAC current was a non-selective cation current (ISAC,NC). The background current was also found to be non-selective to cations (INSC,b); the permeability ratio ( PCs: PNa: PLi= 1·49:1:0·70) was different from that of ISAC,NC., Gadolinium (Gd3+) acted on INSC,b and ISAC,NC differently. Gd3+ inhibited INSC,b in a concentration-dependent manner with an IC50 value of 46·2 ± 0·8 μM ( n= 5). Consistent with this effect, Gd3+ hyperpolarised the resting membrane potential (-71·1 ± 0·26 mV, n= 9). In the presence of Gd3+ (0·1 mM), stretch still induced ISAC,NC and diastolic depolarisation., Single-channel activities were recorded in isotonic Na+ and Cs+ solutions using the inside-out configuration. In NMDG+ solution, outward currents were abolished. Gd3+ (100 μM) strongly inhibited channel opening both from the inside and outside. In the presence of Gd3+ (100 μM) in the pipette solution, an increase in pipette pressure induced an increase in channel opening (21·27 ± 0·24 pS; n= 7), which was distinct from background activity., We concluded from the above results that longitudinal stretch in rat atrial myocytes induces the activation of non-selective cation channels that can be distinguished from background channels by their different electrophysiology and pharmacology.
- Publication
Journal of Physiology, 2000, Vol 523, Issue 3, p607
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1111/j.1469-7793.2000.00607.x