Comparison of Ca2+ Currents of Chromaffin Cells from Normotensive Wistar Kyoto and Spontaneously Hypertensive Rats

Abstract

Spontaneously hypertensive rats (SHR) are widely used as model to investigate the pathophysiological mechanisms of essential hypertension. Catecholamine plasma levels are elevated in SHR, suggesting alterations of the sympathoadrenal axis. The residual hypertension in sympathectomized SHR is reduced after demedullation, suggesting a dysfunction of the adrenal medulla. Intact adrenal glands exposed to acetylcholine or high K+ release more catecholamine in SHR than in normotensive Wistar Kyoto (WKY) rats, and adrenal chromaffin cells (CCs) from SHR secrete more catecholamines than CCs from WKY rats. Since Ca2+ entry through voltage-gated Ca2+ channels (VGCC) triggers exocytosis, alterations in the functional properties of these channels might underlie the enhanced catecholamine release in SHR. This study compares the electrophysiological properties of VGCC from CCs in acute adrenal slices from WKY rats and SHR at an early stage of hypertension. No significant differences were found in the macroscopic Ca2+ currents (current density, I–V curve, voltage dependence of activation and inactivation, kinetics) between CCs of SHR and WKY rats, suggesting that Ca2+ entry through VGCC is not significantly different between these strains, at least at early stages of hypertension. Ca2+ buffering, sequestration and extrusion mechanisms, as well as Ca2+ release from intracellular stores, must now be evaluated to determine if alterations in their function can explain the enhanced catecholamine secretion reported in CCs from SHR.

Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices

“…In previous papers, we characterized the Ca 2+ ‐currents expressed in acute adrenal slices (Segura‐Chama et al . , ; Hernández et al . ), Now, we identify the Ca 2+ ‐channel subtypes that control the activation of Ca 2+ ‐activated K + ‐channels after Ca 2+ ‐influx.…”

“…Second, when Na + ‐current was blocked, Ca 2+ ‐channels participated alone in generating APs of less amplitude; however, these reduced spontaneous APs cease after several seconds, presumably by inactivation of Ca 2+ ‐channels. Despite our report that no T‐type channels are detected in adult CCs of both mouse and SHR/WKY rats (Segura‐Chama et al ., ;2011; Hernández et al ., ), it has been shown that in cultured RCCs under sustained adrenergic stimulation, low‐voltage‐activated Ca 2+ channels are expressed and, following a lowered threshold of AP firing, may increase cell excitability during sustained sympathetic stimulation (Novara et al . ).…”

Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the α1D Ca2+ channel

“…Our laboratory recently compared the electrophysiological properties of voltage-gated Ca 2ϩ currents (I Ca ) in adrenal chromaffin cells (CCs) from WKY rats and SHR to determine whether the catecholamine hypersecretion reported in CCs from the SHR strain (27,28) was due to an augmented function of voltage-gated Ca 2ϩ channels. Our results showed that the electrophysiological and pharmacological properties of I Ca in adrenal CCs from SHR and WKY are indistinguishable (39), implying that catecholamine hypersecretion in SHR CCs cannot be attributed to augmented Ca 2ϩ entry, and also that the choice of the WKY strain as control was appropriate in this case. Nonetheless, we noticed differences in the kinetics and voltage dependence of I Ca recorded from CCs of the WKY/SHR strains compared with those recorded under the same conditions from adrenal CCs of other normotensive strains, e.g., Wistar rat and Balb-C mice (11,12,35), and we wondered if these differences in kinetics and voltage dependence could be of physiological significance.…”

“…In the remaining sections, we focus on the electrophysiological properties of I Ca in WKY and SHR CCs. Our laboratory has previously shown that activation and inactivation kinetics, current density, voltage dependence of activation and inactivation, involvement of L-type Ca 2ϩ channels in the total I Ca , and autocrine modulation of I Ca in CCs from WKY and SHR rats are virtually indistinguishable (39).…”

Effects of chronic dietary salt loading on the renin angiotensin and adrenergic systems of rainbow trout (Oncorhynchus mykiss)

“…Upon cessation of voluntary swimming movements (but before breathing had stopped), the trout were removed from anesthetic, weighed, and transferred to a surgical table where the gills were irrigated continuously with the same anesthetic solution for the duration of the surgery. To permit the measurement of dorsal aortic blood pressure (P DA) and blood sampling, and to permit injections of drugs (in the event of venous cannula failure), an indwelling polyethylene cannula (PE-50; Clay-Adams) was implanted into the dorsal aorta via percutaneous puncture (61). The cannula was flushed with chilled heparinized (50 U/ml ammonium heparin) Cortland saline (69) and sealed with a needle.…”