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Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.

ABSTRACT: Expression of thrombospondin-4 (TSP-4), a matricellular protein, is increased in the heart tissue of various cardiac disease models. In dorsal root ganglion neurons, TSP-4 inhibits L-type Ca2+ channel (LTCC) activity. Although TSP-4 might be related to the electrophysiological properties in heart, it remains to be clarified. The present study aimed to clarify the effects of TSP-4 on action potential (AP), LTCC current (ICaL) and voltage-dependent K+ (Kv) channel current (IKv) in rat isolated ventricular myocytes by a patch clamp technique. Ventricular myocytes were isolated from the heart of adult male Wistar rats. The ventricular myocytes were treated with TSP-4 (5 nM) or its vehicle for 4 hr. Then, whole-cell patch clamp technique was performed to measure AP (current-clamp mode) and ICaL and IKv (voltage-clamp mode). The mRNA expression of Kv channels was examined by reverse transcription-polymerase chain reaction. TSP-4 had no effect on the resting membrane potential and peak amplitude of AP. On the other hand, TSP-4 significantly prolonged AP duration (APD) at 50% and 90% repolarization. TSP-4 significantly inhibited the peak amplitudes of ICaL and IKv. TSP-4 had no effect on mRNA expression of Kv channels (Kcna4, Kcna5, Kcnb1, Kcnd2 and Kcnd3). The present study for the first time demonstrated that TSP-4 prolongs APD in rat ventricular myocytes, which is possibly mediated through the suppression of Kv channel activity.

SUBMITTER: Imoto K

PROVIDER: S-EPMC7324826 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.

Imoto Keisuke K Aratani Momoko M Koyama Takahiro T Okada Muneyoshi M Yamawaki Hideyuki H

The Journal of veterinary medical science 20200403 6

Expression of thrombospondin-4 (TSP-4), a matricellular protein, is increased in the heart tissue of various cardiac disease models. In dorsal root ganglion neurons, TSP-4 inhibits L-type Ca2+ channel (LTCC) activity. Although TSP-4 might be related to the electrophysiological properties in heart, it remains to be clarified. The present study aimed to clarify the effects of TSP-4 on action potential (AP), LTCC current (ICaL) and voltage-dependent K+ (Kv) channel ...[more]

PMID: 32249254

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Project description:"Physiological" aging as well as early and progressive cardiac hypertrophy may affect action potential (AP) pattern, contractile function, and Ca(2+) handling. We hypothesize that contractile function is disturbed in hypertrophy from early stages and is differently affected in aged myocardium. In vivo function, cardiomyocyte contractile behavior and APs were compared in Wistar-Kyoto (WIS) rats and spontaneously hypertensive rats (SHR) at different ages and degrees of hypertrophy (3-4, 9-11, 20-24 months). Post-rest (PR) behavior was used to investigate the relative contribution of the sarcoplasmic reticulum (SR) and the Na/Ca exchanger (NCX) to cytosolic Ca(2+) removal. APs were recorded by whole-cell current-clamp and sarcomere shortening by video microscopy. Cyclopiazonic acid was used to suppress Ca(2+) ATPase (SERCA) function. Heart weight/body weight ratio was increased in SHR versus WIS within all age groups. Myocyte steady state (SS) shortening amplitude was reduced in young SHR versus WIS. Aging led to a significant decay of SS contractile amplitude and relengthening velocity in WIS, but the PR potentiation was maintained. In contrast, aging in SHR led to a decrease of PR potentiation, while SS contraction and relengthening velocity increased. APD(50%) was always prolonged in SHR versus WIS. With aging, APD(50%) increased in both WIS and SHR, but was still shorter in WIS. However, in old WIS the late AP portion (APD(90%)) was prolonged. Ca(2+) handling and AP properties are disturbed progressively with aging and with increasing hypertrophy. Decreased amplitude of shortening and velocity of relengthening in aged WIS may be attributed to reduced SERCA function. In SHR, an increase in SR leak and shift towards transmembraneous Ca handling via NCX may be responsible for the changes in contractile function. A prolonged APD(90%) in aged WIS may be an adaptive mechanism to preserve basal contractility. Therefore, the effects on contractile parameters and AP are different in hypertrophy and aging.

Dataset Information

Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.

Publications

Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.

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