Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias

Kushner, Jared; Ferrer, Xavier; Marx, Steven O.

doi:10.19102/icrm.2019.101006

Cited by 9 publications

(8 citation statements)

References 68 publications

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“…So far, more limited studies have been performed on modeling the gastrointestinal tract than the heart. While different models have been suggested for the heart, including electrophysiological, electrochemical, three-dimensional, FEM, and quantitative (13,27,28). Finally, considering the results of this study, pacemakers may be designed to control the contractile activity of the gastric smooth muscle, such as the heart (7,29).…”

Section: Discussionmentioning

confidence: 88%

The Role of Potassium Channel Gates in the Electrophysiology of the Human Gastric Smooth Muscle Cell

et al. 2022

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Background: The cell membrane acts as a filter, allowing ions to enter and leave the cell. Ionic channels are responsible for passing ions. This task is the responsibility of the ion channel gates, and ion transfer generates the action potential. Potassium channels play a prominent role in gastrointestinal smooth muscle cells and slow-wave production. Potassium channels are involved in acid secretion and gastric contraction. Gastric functional problems such as reflux disease and motility disorder are classified as electrophysiological disorders. Objectives: This study aimed to investigate the effect of potassium channel gates on the electrophysiology of the human gastric smooth muscle cells. Methods: Three states were considered for the potassium channels gate (Including physiological state, 50% blockage, and 90% blockage) to investigate the effect of the status of the gates, and a slow-wave diagram was obtained in these three states. Then, the value and the time of action potential were compared at five indicator points (initial potential, maximum spike potential, minimum valley potential, maximum plateau potential, and resting potential) in slow-wave. Results: The results showed that the maximum effect of the activation parameter of the potassium channel gate (τd,Kni) was in 90% blockage compared to the physiological state, so that the maximum spike potential decreases by 2.43%. Also, a 90% blockage in the fast potassium channel gate inactivation parameter (τf,Kfi) increased the maximum spike potential by 12.6% compared to the physiological state, while the minimum valley potential increased by 3%. In addition, the τf,Kfi parameter reduced the time of occurrence of the maximum plateau potential by 7.9%. Conclusions: Potassium channels affect the slow-wave of the human gastric smooth muscle cell in spike, valley, and plateau phases. Using this method and blocking ion channels by pharmacological agents, the effect of ions in different phases of the slow-wave can be investigated. Also, it can help improve the contractile and motility disorders of the smooth muscles of the gastrointestinal tract.

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Section: Discussionmentioning

confidence: 88%

The Role of Potassium Channel Gates in the Electrophysiology of the Human Gastric Smooth Muscle Cell

et al. 2022

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“…Voltage-dependent calcium channel subunit alpha2delta2 (CACNA2D) is known to be responsible for regulating calcium transportation and signal responses in cardiomyocytes [ 96 ], and it has been reported that miR-1231 aggravates arrhythmia by targeting CACNA2D2 [ 97 ]. Considering that the dysfunction of calcium channels has been closely associated with cardiac hypertrophy, arrhythmias, or even heart failure [ 98 ], it is likely that the increase in miR-1231 in EAT imposes potential harm to the heart.…”

Section: Micrornas Expressed In Human Eatmentioning

confidence: 99%

The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review

Kim

Song

Lim

et al. 2023

Biology

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Cardiovascular diseases have been leading cause of death worldwide for many decades, and obesity has been acknowledged as a risk factor for cardiovascular diseases. In the present review, human epicardial adipose tissue-derived miRNAs reported to be differentially expressed under pathologic conditions are discussed and summarized. The results of the literature review indicate that some of the epicardial adipose tissue-derived miRNAs are believed to be cardioprotective, while some others show quite the opposite effects depending on the underlying pathologic conditions. Furthermore, they suggest that that the epicardial adipose tissue-derived miRNAs have great potential as both a diagnostic and therapeutic modality. Nevertheless, mainly due to highly limited availability of human samples, it is very difficult to make any generalized claims on a given miRNA in terms of its overall impact on the cardiovascular system. Therefore, further functional investigation of a given miRNA including, but not limited to, the study of its dose effect, off-target effects, and potential toxicity is required. We hope that this review can provide novel insights to transform our current knowledge on epicardial adipose tissue-derived miRNAs into clinically viable therapeutic strategies for preventing and treating cardiovascular diseases.

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“…Depending on the pharmacological sensitivity and activation rate, so far, six types of calcium channels have been observed. These include T, L, N, P, Q, and R types [ 23 ], which are named according to their responses to the voltage applied. The most significant calcium channel subtypes are L-type and T-type, which play key roles in regulating heart functions.…”

Section: Calcium Channelsmentioning

confidence: 99%

“…Both L-type and T-type are voltage-gated. L-type channels are long-lasting and their activation requires resilient depolarization, whereas T-type channels are transient [ 23 ]. A comprehensive understanding of the structural properties of these channels opens a wider pathway through which to identify their importance in cardiovascular pathologies.…”

Section: Calcium Channelsmentioning

confidence: 99%

“…The same research group has contributed enormously to the synthesis of DHPs and DHPMs [ 65 , 66 ]. They have attempted to synthesize CCBs, which could mimic ones which are of clinical use [ 4 , 21 , 22 , 23 , 24 , 25 , 27 ]. Several other modifications, such as triazole ligation, which introduce nitrile, carboxylic, and hydrazide groups and amino acid coupling reactions were investigated in order to obtain the compounds listed in Table 2 [ 67 ].…”

Section: Synthesis Of Dihydropyrimidinesmentioning

confidence: 99%

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Synthesis of Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their Calcium Channel Blocking Efficiency

et al. 2023

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Hypertension and cardiovascular diseases related to it remain the leading medical challenges globally. Several drugs have been synthesized and commercialized to manage hypertension. Some of these drugs have a dihydropyrimidine skeleton structure, act as efficient calcium channel blockers, and affect the calcium ions’ intake in vascular smooth muscle, hence managing hypertension. The synthesis of such moieties is crucial, and documenting their structure–activity relationship, their evolved and advanced synthetic procedures, and future opportunities in this area is currently a priority. Tremendous efforts have been made after the discovery of the Biginelli condensation reaction in the synthesis of dihydropyrimidines. From the specific selection of Biginelli adducts to the variation in the formed intermediates to achieve target compounds containing heterocylic rings, aldehydes, a variety of ketones, halogens, and many other desired functionalities, extensive studies have been carried out. Several substitutions at the C3, C4, and C5 positions of dihydropyrimidines have been explored, aiming to produce feasible derivatives with acceptable yields as well as antihypertensive activity. The current review aims to cover this requirement in detail.

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Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias

Cited by 9 publications

References 68 publications

The Role of Potassium Channel Gates in the Electrophysiology of the Human Gastric Smooth Muscle Cell

The Role of Potassium Channel Gates in the Electrophysiology of the Human Gastric Smooth Muscle Cell

The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review

Synthesis of Dihydropyrimidines: Isosteres of Nifedipine and Evaluation of Their Calcium Channel Blocking Efficiency

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