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Updated: May 12, 2026

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Published on: October 15, 2014
Functional integrity of the T-tubular system in cardiomyocytes depends on p21-activated kinase 1
Jaime DeSantiago1, Dan J Bare, Yunbo Ke
1Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL 60612, USA.
Abstract:
p21-activated kinase (Pak1), a serine-threonine protein kinase, regulates cytoskeletal dynamics and cell motility. Recent experiments further demonstrate that loss of Pak1 results in exaggerated hypertrophic growth in response to pathophysiological stimuli. Calcium (Ca) signaling plays an important role in the regulation of transcription factors involved in hypertrophic remodeling. Here we aimed to determine the role of Pak1 in cardiac excitation-contraction coupling (ECC). Ca transients were recorded in isolated, ventricular myocytes (VMs) from WT and Pak1(-/-) mice. Pak1(-/-) Ca transients had a decreased amplitude, prolonged rise time and delayed recovery time. Di-8-ANNEPS staining revealed a decreased T-tubular density in Pak1(-/-) VMs that coincided with decreased cell capacitance and increased dis-synchrony of Ca induced Ca release (CICR) at individual release units. These changes were not observed in atrial myocytes of Pak1(-/-) mice where the T-tubular system is only sparsely developed. Experiments in cultured rabbit VMs supported a role of Pak1 in the maintenance of the T-tubular structure. T-tubular density in rabbit VMs significantly decreased within 24h of culture. This was accompanied by a decrease of the Ca transient amplitude and a prolongation of its rise time. However, overexpression of constitutively active Pak1 in VMs attenuated the structural remodeling as well as changes in ECC. The results provide significant support for a prominent role of Pak1 activity not only in the functional regulation of ECC but for the structural maintenance of the T-tubular system whose remodeling is an integral feature of hypertrophic remodeling.
Insights
p21-activated kinase (Pak1) is crucial for maintaining cardiac excitation-contraction coupling and T-tubular structure. Loss of Pak1 impairs calcium handling and leads to hypertrophic remodeling in heart cells.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
- Molecular Cardiology
Background:
- p21-activated kinase (Pak1) regulates cytoskeletal dynamics and cell motility.
- Pak1 deficiency leads to exaggerated hypertrophic growth.
- Calcium (Ca) signaling is vital for cardiac hypertrophic remodeling.
Purpose of the Study:
- To investigate the role of Pak1 in cardiac excitation-contraction coupling (ECC).
- To determine Pak1's involvement in maintaining the T-tubular system structure.
Main Methods:
- Recorded Ca transients in ventricular myocytes (VMs) from wild-type (WT) and Pak1(-/-) mice.
- Utilized Di-8-ANNEPS staining to assess T-tubular density.
- Performed experiments in cultured rabbit VMs, including Pak1 overexpression.
Main Results:
- Pak1(-/-) VMs exhibited decreased Ca transient amplitude, prolonged rise time, and delayed recovery.
- Reduced T-tubular density and increased Ca release desynchrony were observed in Pak1(-/-) VMs.
- Pak1 activity was essential for T-tubular structural maintenance and attenuated remodeling in VMs.
Conclusions:
- Pak1 plays a significant role in the functional regulation of cardiac ECC.
- Pak1 is critical for the structural integrity of the T-tubular system.
- Pak1 activity is integral to preventing hypertrophic remodeling of cardiac myocytes.
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