Cardiac electrical activity elsewhere than in ventricular muscle cells
Burt B. Hamrell in Cardiovascular Physiology, 2018
Four sarcolemmal ionic currents and intracellular Ca2+ cycling contribute to SA node diastolic depolarization during phase 4. If is a depolarizing current during phase 4. If channels support the slow movement inward of primarily Na+. It is a peculiar ion channel (“f” stands for funny) in that it is activated by repolarization. Other voltage-gated channels are activated by depolarization. This channel also is referred to as the HCN channel: hyperpolarization-activated, cyclic nucleotide gated channel. As noted above, the onset of If at the end of phase 3 repolarization is one reason why the MDP is less negative than in non-nodal myocytes. Another reason is the minimal expression of K1 channels in nodal myocytes.Three Na+/1 Ca2+ exchange (NCX) contributes to depolarization during phase 4 and NCX is related to cyclic changes in myocyte myoplasmic Ca2+ content. As noted above, phase 0 is due to the opening of L-type Ca2+ channels. The entry of Ca2+ into the cell initiates Ca2+-induced-Ca2+-release from the ryanodine-sensitive Ca2+-release channels on the terminal cisternae of the sarcoplasmic reticulum (SR).
Nonclassical Ion Channels in Depression
Tian-Le Xu, Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
The HCN channel is primarily expressed in the brain, heart, and retina3, and modulates neuronal excitability and activity through a hyperpolarization-activated current (Ih) consisting of Na+ and K+ cations4,5. HCN channels are voltage-gated and modulated by the endogenous ligand cyclic adenosine 3’,5’-monophosphate (cAMP), the opening of which (typically at potentials below −50 mV) causes membrane depolarization and decreases membrane resistance. Neuronal network activity can be affected by HCN expression levels, its localization to subcellular compartments, and the composition of its subunits6. Given the role of Ih and HCN channels in controlling synaptic transmission and rhythmic oscillatory activity in the brain7, disruption of HCN channel function can be involved in the development of depression or targeted as a therapeutic strategy.
Restoration of Membrane Environments for Membrane Proteins for Structural and Functional Studies
Qiu-Xing Jiang in New Techniques for Studying Biomembranes, 2020
To use the cryo-EM method to assess the transmembrane potential, cryo-EM images of liposomes were circularly averaged and compared with that of a simulated liposome. As shown in Figure 8.4d, the membrane profile including a positive transmembrane potential fits the experimental profile better than that without the positive transmembrane potential. As the effect of the transmembrane potential on the circularly averaged liposome intensity is less obvious compared with that of the dipole potential (Figures 8.3e and 8.4c), the accuracy of the transmembrane potential measured using this method is less than that of the dipole potential measurement. Another way to assess the transmembrane potential is to study the effect of the transmembrane potential on the structure of the HCN2 channel using the RSC method. As shown in Section 3.1, HCN2 channels open at −120 mV and close at −90 mV. If the structure of HCN channel at −120 mV is different from that at −90 mV, then the magnitude of the transmembrane potential is confirmed (the inside-out inserted HCN2 channels experience a negative transmembrane potential with the setting shown in Figure 8.4a).
Ivabradine, the hyperpolarization-activated cyclic nucleotide-gated channel blocker, elicits relaxation of the human corpus cavernosum: a potential option for erectile dysfunction treatment
Published in The Aging Male, 2020
Serap Gur, Laith Alzweri, Didem Yilmaz-Oral, Ecem Kaya-Sezginer, Asim B. Abdel-Mageed, Suresh C. Sikka, Wayne J. G. Hellstrom
Also, in this study, the specific type Ca2+ channel blocker, nifedipine, and the nonselective K+ channel blocker, TEA, significantly inhibited ivabradine-induced relaxation in HCC. Thus, it can be proposed that other mechanisms, such as the effect on Ca2+ and K+ channels in penile smooth muscle, may play a prominent role. Ivabradine partially facilitates HCC muscle relaxation through different mechanisms, depending on several ion channels and independent of the classical NO/sGC pathway. Ca2+-related pathways may enable persistent activity at the single-cell level through hyperpolarization-activated HCN channels [38,39]. The HCN channel releases Ca2+ from the sarcoplasmic reticulum in atrioventricular node conduction. The inhibition of If channels blocked Ca2+ release and delayed conduction in functional experiments [40]. Also, silencing of HCN4 channel caused altered Ca2+ release and Ca2+ handling in the sinoatrial node, which leads to impaired pacemaker activity and symptoms characteristic of human pacemaking [41]. Previous studies have demonstrated that the If channel improved membrane potential and contributed to the generation of rhythmic cardiac activity, which reveals a mixed permeability to both Na+ and K+ channels[42,43].
Role of ivabradine and heart rate lowering in chronic heart failure: guideline update
Published in Expert Review of Cardiovascular Therapy, 2018
Sheryl L Chow, Robert L. Page, Christophe Depre
Ivabradine crosses the SAN pacemaker cell plasma membrane and selectively blocks the gated HCN channel from its inner rim by binding to a site located in the inner cavity of the HCN channel, resulting in a dose-dependent reduction in If [42,50–53]. Ultimately, through reduction of the ionic current, the diastolic depolarization phase of the SAN action potential is prolonged, leading to heart rate reduction (Figure 1) [50,51]. This mechanism of action is termed ‘use dependency’ because there is a proportional relationship between the abundance of ion flow change and ivabradine binding. As heart rate increases, ivabradine has greater access to the HCN4 channel. Therefore, the amplitude of ivabradine-mediated heart rate reduction is proportional to the baseline heart rate (the higher the heart rate, the higher heart rate reduction). Furthermore, ivabradine selectively slows heart rate without affecting left ventricular relaxation or contractility [42–44].
Correlation between HCN4 gene polymorphisms and lone atrial fibrillation risk
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Xiao-Hong Li, Ya-Min Hu, Guang-Li Yin, Ping Wu
HCN belongs to voltage-gated cation channel family, including four subunits (HCN1-4). In the atrial tissues, HCN4 is the main subunit. Voltage dependence and the permeability of K+ and Na+ are the mainly electrophysiological properties of HCN channel. In addition, HCN4 could regulate the funny current. Thus, we considered that the polymorphisms in HCN4 gene might affect the atrial potential, thus influencing the occurrence of AF. We selected two SNPs which were with the minor allele frequencies (MAF) more than 0.05 in the intron region of HCN4 gene to explore the association of HCN4 SNPs with lone AF risk and ALP of the patients.
Related Knowledge Centers
- Protein
- Heart
- Cell Membrane
- Brain
- Ion Channel
- Functional Selectivity
- Voltage-Gated Ion Channel
- Ion
- Gene
- Hcn1