Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Comparison of spin-wave modes in connected and disconnected artificial spin ice nanostructures using Brillouin light scattering spectroscopy

Artificial spin ice systems have seen burgeoning interest due to their intriguing physics and potential applications in reprogrammable memory, logic, and magnonics. Integration of artificial spin ice with functional magnonics is a relatively recent research direction, with a host of promising results. As the field progresses, direct in-depth comparisons of distinct artificial spin systems are crucial to advancing the field. While studies have investigated the effects of different lattice geometries, little comparison exists between systems comprising continuously connected nanostructures, where spin-waves propagate via dipole-exchange interaction, and systems with nanobars disconnected at vertices, where spin-wave propagation occurs via stray dipolar field. Gaining understanding of how these very different coupling methods affect both spin-wave dynamics and magnetic reversal is key for the field to progress and provides crucial system-design information including for future systems containing combinations of connected and disconnected elements. Here, we study the magnonic response of two kagome spin ices via Brillouin light scattering, a continuously connected system and a disconnected system with vertex gaps. We observe distinct high-frequency dynamics and magnetization reversal regimes between the systems, with key distinctions in spin-wave localization and mode quantization, microstate trajectory during reversal and internal field profiles. These observations are pertinent for the fundamental understanding of artificial spin systems and broader design and engineering of reconfigurable functional magnonic crystals