An intercellular regenerative calcium wave in porcine coronary artery endothelial cells in primary culture

Salomonsson

et al. 2004

British J Pharmacology

In this study, intracellular Ca2+ was measured as the Fura‐2 ratio (R) of fluorescence excited at 340 and 380 nm (F340/F380) in nonpressurized rat mesenteric small arterioles (Ø (lumen diameter) 10–25 μm). The response to depolarization using 75 mM KCl was an increase in R from a baseline of 0.96±0.01 ([Ca2+]i ∼74 nM) to 1.04±0.01 (∼128 nM) (n=80). The response to 75 mM K+ was reversibly abolished in Ca2+‐free physiological saline solution, whereas phentolamine (10 μM) or tetrodotoxin (1 μM) had no effects. LaCl3 (200 μM) inhibited 61±9% of the response. A [K+]‐response curve indicated that the Ca2+ response was activated between 15 and 25 mM K+. The data suggest that the Ca2+ response was caused by the activation of voltage‐dependent Ca2+ channels. Mibefradil use dependently inhibited the Ca2+ response to 75 mM K+ by 29±2% (100 nM), 73±7% (1 μM) or 89±7% (10 μM). Pimozide (500 nM) use dependently inhibited the Ca2+ response by 85±1%. Nifedipine (1 μM) inhibited the Ca2+ response to 75 mM K+ by 41±12%. The response was not inhibited by calciseptine (500 nM), ω‐agatoxin IVA (100 nM), ω‐conotoxin MVIIA (500 nM), or SNX‐482 (100 nM). Using reverse transcriptase–polymerase chain reaction, it was shown that neither CaV2.1a (P‐type) nor CaV2.1b (Q‐type) voltage‐dependent Ca2+ channels were expressed in mesenteric arterioles, whereas the CaV3.1 (T‐type) channel was expressed. Furthermore, no amplification products were detected when using specific primers for the β1b, β2, or β3 auxiliary subunits of high‐voltage‐activated Ca2+ channels. The results suggest that the voltage‐dependent Ca2+ channel activated by sustained depolarization in mesenteric arterioles does not classify as any of the high‐voltage‐activated channels (L‐, P/Q‐, N‐, or R‐type), but is likely to be a T‐type channel. The possibility that the sustained Ca2+ influx observed was the result of a T‐type window current is discussed. British Journal of Pharmacology (2004) 142, 709–718. doi:10.1038/sj.bjp.0705841

Section: Basal Characteristics Of the Kcl-induced Ca 2 þ Responsementioning

confidence: 87%

Depolarization‐induced calcium influx in rat mesenteric small arterioles is mediated exclusively via mibefradil‐sensitive calcium channels

Salomonsson

et al. 2004

British J Pharmacology

American Journal of Physiology-Heart and Circulatory Physiology

“…To examine effects of gap junction inhibitors on "baseline" vascular tone and hypoxic vasoconstriction in meclofenamate-and L-NNA-pretreated normotensive and hypertensive lungs, 30 M 18␣-glycyrrhetinic acid (Sigma) (10,29), 50 M palmitoleic acid (Sigma) (3,13,27,56), or vehicle (DMSO) was added to the perfusate according to the above protocol for CYP450 inhibitors. The lungs were then challenged twice with 15 min of 3% O 2 at 15 and 40 min after the gap junction inhibitors or vehicle.…”

Section: Methodsmentioning

confidence: 99%

“…The incidence of myoendothelial gap junctions is higher in resistance than in conduit arteries (46). Putative gap junction inhibitors, such as palmitoleic acid (13,27,56), 18␣-glycyrrhetinic acid (10,16,23,27,29,36,52,53), and Gap 27 (9,16,47,52), a synthetic peptide with sequence homology to a region of the second extracellular loop of Cx37 and Cx43, reduce EDHF-mediated hyperpolarization and relaxation in various arteries. These observations suggest that the EDHF signal represents electrotonic spread of hyperpolarization from the endo-thelium into the medial smooth muscle via myoendothelial and homocellular smooth muscle gap junctions.…”

mentioning

confidence: 99%

EDHF-mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs

Morio

Carter

Oka

et al. 2003

. EDHF-mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs. Am J Physiol Heart Circ Physiol 284: H1762-H1770, 2003. First published January 9, 2003 10.1152/ajpheart.00831.2002The role of endothelium-derived hyperpolarizing factor (EDHF) in regulating the pulmonary circulation and the participation of cytochrome P-450 (CYP450) activity and gap junction intercellular communication in EDHF-mediated pulmonary vasodilation are unclear. We tested whether tonic EDHF activity regulated pulmonary vascular tone and examined the mechanism of EDHF-mediated pulmonary vasodilation induced by thapsigargin in salt solution-perfused normotensive and hypoxia-induced hypertensive rat lungs. After blockade of both cyclooxygenase and nitric oxide synthase, inhibition of EDHF with charybdotoxin plus apamin did not affect either normotensive or hypertensive vascular tone or acute hypoxic vasoconstriction but abolished thapsigargin vasodilation in both groups of lungs. The CYP450 inhibitors 7-ethoxyresorufin and sulfaphenazole and the gap junction inhibitor palmitoleic acid, but not 18␣-glycyrrhetinic acid, inhibited thapsigargin vasodilation in normotensive lungs. None of these agents inhibited the vasodilation in hypertensive lungs. Thus tonic EDHF activity does not regulate either normotensive or hypertensive pulmonary vascular tone or acute hypoxic vasoconstriction. Whereas thapsigargin-induced EDHF-mediated vasodilation in normotensive rat lungs involves CYP450 activity and might act through gap junctions, the mechanism of vasodilation is apparently different in hypertensive lungs. pulmonary vasoregulation; pulmonary hypertension; endothelium-derived hyperpolarizing factor; cytochrome P-

J Cereb Blood Flow Metab

“…Although this could be influenced by the choice of model or anestethic agent, we would argue that conducted hyperpolarizations along the endothelial pathway leading to remote dilatations, cannot explain the phenomenon of CSDs. Much slower intercellular Ca 2 þ waves have been described in ECs in culture, 89 in isolated vessels, 17 and in vivo. 16 The intercellular Ca 2 þ waves are dependent on the PLC pathway, IP 3 diffusion, Ca 2 þ -induced Ca 2 þ release, and gap junctions.…”

Section: Potential Role Of Vascular Conducted Responses In Cerebrovasmentioning

confidence: 99%

The Vascular Conducted Response in Cerebral Blood Flow Regulation

Jensen¹,

Holstein‐Rathlou

2013

Despite recent advances in our understanding of the molecular and cellular mechanisms behind vascular conducted responses (VCRs) in systemic arterioles, we still know very little about their potential physiological and pathophysiological role in brain penetrating arterioles controlling blood flow to the deeper areas of the brain. The scope of the present review is to present an overview of the conceptual, mechanistic, and physiological role of VCRs in resistance vessels, and to discuss in detail the recent advances in our knowledge of VCRs in brain arterioles controlling cerebral blood flow. We provide a schematic view of the ion channels and intercellular communication pathways necessary for conduction of an electrical and mechanical response in the arteriolar wall, and discuss the local signaling mechanisms and cellular pathway involved in the responses to different local stimuli and in different vascular beds. Physiological modulation of VCRs, which is a rather new finding in this field, is discussed in the light of changes in plasma membrane ion channel conductance as a function of health status or disease. Finally, we discuss the possible role of VCRs in cerebrovascular function and disease as well as suggest future directions for studying VCRs in the cerebral circulation.