Reviews of Physiology, Biochemistry and Pharmacology, 2014
Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key ... more Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.
The Cav2.3 voltage-gated calcium channel represents the most enigmatic of all voltage-gated calci... more The Cav2.3 voltage-gated calcium channel represents the most enigmatic of all voltage-gated calcium channels due to its pharmacological inertness and to its mixed characteristics of HVA and LVA calcium channels. Protein interaction partners of the cytosolic II-III linker of Cav2.3 contribute to calcium homeostasis by regulating the channels surface expression and activation. Specific regulation of Cav2.3 by proteins interacting with the carboxy terminal region plays an important role in exocytosis and presynaptic plasticity, linking channel function to long-term potentiation. Modulation of Cav2.3 by its interaction partners thus contributes to several physiologic processes such as signal transduction in the retina, insulin secretion and generation of rhythmic activity in the heart and in the brain.
A worrisome number of approximately one million pregnant women in sub-Saharan Africa are affected... more A worrisome number of approximately one million pregnant women in sub-Saharan Africa are affected by malaria and HIV/AIDS annually. To assess the effects of co-infection with these diseases, clinical, parasitological and haematological data were obtained and analysed from 399 pregnant women from Douala and Muyuka. HIV/AIDS, malaria and co-infection prevalence rates were respectively 21.1% (84/399), 86.5% (345/399) and 17.3% (69/399). Co-infected pregnant women presented with higher geometric mean parasitaemia (8 135) per µl of blood (U=857.5, p=0.10) and a significantly lower mean haemoglobin (10.68 ±0.33) g/dL (χ2=7.87, p=0.04) when compared with women in the other disease categories. Generally, median CD4+ counts were lower in the co-infected (332) when compared with HIV/AIDS patients (454) (U=27.5, p=0.17). More co-infected patients had moderate and low CD4+ counts (χ2=10.16, p=0.12). Out of the 69 co-infected patients, 42 (60.9%) had anaemia and of these 30 (71.4%) had moderate ...
Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contracti... more Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation.
Reviews of Physiology, Biochemistry and Pharmacology, 2014
Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key ... more Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.
Reviews of Physiology, Biochemistry and Pharmacology, 2014
Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key ... more Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.
The Cav2.3 voltage-gated calcium channel represents the most enigmatic of all voltage-gated calci... more The Cav2.3 voltage-gated calcium channel represents the most enigmatic of all voltage-gated calcium channels due to its pharmacological inertness and to its mixed characteristics of HVA and LVA calcium channels. Protein interaction partners of the cytosolic II-III linker of Cav2.3 contribute to calcium homeostasis by regulating the channels surface expression and activation. Specific regulation of Cav2.3 by proteins interacting with the carboxy terminal region plays an important role in exocytosis and presynaptic plasticity, linking channel function to long-term potentiation. Modulation of Cav2.3 by its interaction partners thus contributes to several physiologic processes such as signal transduction in the retina, insulin secretion and generation of rhythmic activity in the heart and in the brain.
A worrisome number of approximately one million pregnant women in sub-Saharan Africa are affected... more A worrisome number of approximately one million pregnant women in sub-Saharan Africa are affected by malaria and HIV/AIDS annually. To assess the effects of co-infection with these diseases, clinical, parasitological and haematological data were obtained and analysed from 399 pregnant women from Douala and Muyuka. HIV/AIDS, malaria and co-infection prevalence rates were respectively 21.1% (84/399), 86.5% (345/399) and 17.3% (69/399). Co-infected pregnant women presented with higher geometric mean parasitaemia (8 135) per µl of blood (U=857.5, p=0.10) and a significantly lower mean haemoglobin (10.68 ±0.33) g/dL (χ2=7.87, p=0.04) when compared with women in the other disease categories. Generally, median CD4+ counts were lower in the co-infected (332) when compared with HIV/AIDS patients (454) (U=27.5, p=0.17). More co-infected patients had moderate and low CD4+ counts (χ2=10.16, p=0.12). Out of the 69 co-infected patients, 42 (60.9%) had anaemia and of these 30 (71.4%) had moderate ...
Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contracti... more Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation.
Reviews of Physiology, Biochemistry and Pharmacology, 2014
Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key ... more Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.
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Papers by Etienne Tevoufouet