Table 1.
Differential effect of InsP3 signalling on cardiomyocyte contractility and Ca2+ handling. (Ang II, angiotensin II; ATP, adenosine triphosphate; CaT, Ca2+ transient; CMs, cardiomyocytes; ET-1, endothelin-1; IP3, inositol 1,4,5-trisphosphate; NRVMS, neonatal rat ventricular cardiomyocytes; PE, phenylephrine; SHR, spontaneously hypertensive rat; SR, sarcoplasmic reticulum; WKY, Wistar-Kyoto strain of rat.)
| species | cell type | agonist | observations | reference |
|---|---|---|---|---|
| rat | NRVMs | PE | ↑ frequency of spontaneous CaT in cytosol | [53] |
| IP3 | ↑ Ca2+ spark frequency in cytosol/nucleus | |||
| ↑ number of Ca2+ waves in nucleus | ||||
| mouse | ventricular CMs | Ang II | ↑ CaT | [54] |
| mouse | ventricular CMs | ET-1 | ↑ CaT | [55] |
| human (healthy and failing) | ventricular CMs | ↑ contractility | [31] | |
| ↑ CaT | ||||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| ATP | ↑ after-contractions during resting period | |||
| ET-1 | ↑ rare spontaneous/sustained Ca2+ elevations | |||
| ↓ resting membrane potential | ||||
| ↑ duration of the action potential | ||||
| ↑ frequency of early after-depolarization | ||||
| mouse | ventricular CMs | ET-1 | ↑ contractility | |
| ATP | ↑ CaT | |||
| Ang II | ↑ diastolic [Ca2+]i | |||
| PE | ↑ after-contractions and prolonged contractures | |||
| ↑ extra-systolic and sustained Ca2+ elevations | ||||
| ↓ resting membrane potential | ||||
| ↑ duration of the action potential | ||||
| ↑ frequency of early after-depolarization | ||||
| rat (WKY and SHR) | ventricular CMs | IP3 ester | ↑ contractility | [33] |
| ET-1 | ↑ CaT | |||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| ↑ rate of rise of CaT | ||||
| ↑ diastolic [Ca2+]i | ||||
| ↑ frequency of Ca2+ sparks in the cytosol | ||||
| rat | ventricular CMs | ET-1 | ↑ CaT | [30] |
| IP3 ester | ↑ frequency of extra-systolic Ca2+ elevations | |||
| rat | ventricular CMs | ET-1 | ↓ contractility (2 min post-stimulation) | [34] |
| ↑ contractility (20 min post-stimulation) | ||||
| ↑ rate of contraction (20 min post-stimulation) | ||||
| ↑ CaT (amplitude; rate of rise) (20 min post-stimulation) | ||||
| rabbit | ventricular CMs | IP3 | ↑ Ca2+ leak in the presence of ruthenium red | [52] |
| rabbit | ventricular CMs | IP3 | ↑ frequency of Ca2+ sparks (immediately observed) | [35] |
| ET-1 | ↓ CaT (2 min post-stimulation) | |||
| ↑ CaT (15 min post-stimulation) | ||||
| mouse (healthy and failing) | ventricular CMs | Ang II | ↑ diastolic [Ca2+]i | [56] |
| ↑ CaT | ||||
| mouse (IP3 overexpression) | ventricular CMs | ET-1 | wild-type: | [28] |
| ↑ CaT | ||||
| ↑ SR Ca2+ load | ||||
| ↑ probability of Ca2+ wave occurrence | ||||
| IP3-overexpression: | ||||
| ↓ probability of Ca2+ wave occurrence sustained SR Ca2+ leak | ||||
| IP3-salt | wild-type: | |||
| ↑ frequency of Ca2+ sparks | ||||
| ↓ SR Ca2+ load | ||||
| IP3-overexpression: | ||||
| ↓ frequency of Ca2+ sparks | ||||
| ↓ SR Ca2+ load | ||||
| no Ca2+ puffs were detected | ||||
| unaltered properties of Ca2+ sparks | ||||
| dog (atrial fibrillation) | atrial CMs | ATP | ↑ CaT | [50] |
| ↑ number of Ca2+ transients | ||||
| rat | atrial CMs | ET-1 | ↓ contractility (4 min post-stimulation) | [49] |
| ↑ contractility (as from 8 min post-stimulation) | ||||
| ↓ CaT (4 min post-stimulation) | ||||
| IP3 ester | ↑ CaT (as from 8 min post-stimulation) | |||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| ↑ frequency of Ca2+ sparks | ||||
| rabbit | atrial CMs | ET-1 | ↑ CaT | [32] |
| ↓ decay τ of CaT | ||||
| ↑ time to peak of CaT | ||||
| dog (atrial fibrillation) | atrial CMs | ET-1 | ↑ CaT (in nucleus of diseased animals) | [46] |
| IP3 | ↑ diastolic [Ca2+]i | |||
| rat | atrial CMs | IP3 ester | ↑ CaT | [16] |
| ↑ frequency of Ca2+ sparks | ||||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| mouse | atrial CMs | ET-1 | ↑ CaT | [57] |
| ↑ diastolic [Ca2+]i | ||||
| ↑ frequency of Ca2+ sparks | ||||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| cat | atrial CMs | ET-1 | ↑ CaT (4 min post-stimulation) | [36] |
| ↑ diastolic [Ca2+]i | ||||
| ↑ frequency of Ca2+ sparks (immediately observed) | ||||
| ↑ frequency of extra-systolic Ca2+ elevations | ||||
| atrial/ventricular CMs | IP3 | atrial CMs: | ||
| ↑ frequency of Ca2+ sparks (immediately | ||||
| adenophostin | observed) | |||
| ↑ diastolic [Ca2+]i | ||||
| ↑ diastolic [Ca2+]i and frequency of Ca2+ puffs in the presence of tetracaine | ||||
| ventricular CMs: | ||||
| ⇔ frequency or properties of Ca2+ sparks | ||||
| cat | atrial CMs | IP3 | ↑ diastolic [Ca2+]i | [58] |
| adenophostin | ↑ frequency of Ca2+ sparks | |||
| cat | atrial CMs | PE | ↑ L-type Ca2+ current | [59] |
| rabbit | atrial CMs | caged-IP3 | ↑ CaT | [38] |
| IP3 ester | ↑ diastolic [Ca2+]i | |||
| ↑ frequency of Ca2+ puffs in the presence of tetracaine | ||||
| rabbit (healthy and failing) | atrial/ventricular CMs | Ang II | failing CMs: | [48] |
| ↑ diastolic [Ca2+]i | ||||
| ↓ CaT | ||||
| ↓ SR Ca2+ load | ||||
| healthy CMs: | ||||
| ↑ diastolic [Ca2+]i | ||||
| ↑ CaT | ||||
| caged-IP3 | failing CMs: | |||
| ↓ CaT (in failing CMs) | ||||
| ↑ diastolic [Ca2+]i | ||||
| healthy CMs: | ||||
| ↑ diastolic [Ca2+]i | ||||
| ↑ CaT | ||||
| tetracaine + IP3 | ↑ frequency of Ca2+ puffs in healthy and failing CMs | |||
| mouse | atrial CMs | ET-1 | ↑ frequency of Ca2+ sparks | [37] |
| ↑ SR Ca2+ leak | ||||
| caged-IP3 | ↑ frequency of Ca2+ sparks | |||
| mouse (IP3 overexpression) | atrial CMs | ET-1 | ↑ frequency of Ca2+ sparks | [40] |
| PE | ↑ occurrence of Ca2+ waves |