Short-term insomnia and common cold: A cross-sectional study.

BACKGROUND: The role of insomnia as a symptom of cold has not been fully explored. This study aimed to identify the nature of mild short-term insomnia (MSTI) as a symptom in common cold and examine the relationship between the diagnosis of common cold and MSTI. METHODS: A cross-sectional study was conducted at a clinic in Nagano, Japan. In this study, 32 participants were recruited as common cold patients, and 30 people without common cold were selected as the comparison group who did not have any symptoms of fever, cough, septum, rhinorrhea, or sore throat in this period. RESULTS: About 75% of patients in the common cold group (CCG; 24 of 32) and 33% of total patients in the not common cold group (NCCG; 10 of 30) showed MSTI. The prevalence of MSTI was significantly more frequent in patients in CC (χ2 = 10.854, df = 1, P < .001). MSTI occurred on an average of 1.0 day (SD = 1.4) before the common cold onset and continued for a mean of 2 days (SD = 1.6). The frequency of fever was related to age, but MSTI appeared regardless of age. CONCLUSION: Mild short-term insomnia is a common symptom in common cold.

ß(2)-Adrenergic and M(2)-muscarinic receptors decrease basal t-tubular L-type Ca2+ channel activity and suppress ventricular contractility in heart failure.

L-type Ca(2+) channels (LTCC) play a crucial role in cardiac excitation-contraction coupling. We previously found that in failing ventricular myocytes of mice chronically treated with isoproterenol, basal t-tubular (TT) LTCC activity was halved by activation of protein phosphatase (PP)2A whereas basal surface sarcolemmal (SS) LTCC activity was doubled by inhibition of PP1. Interestingly, chronic treatment of these mice with pertussis toxin almost completely normalized TT and SS LTCC densities and cardiac contractility. In the present study, we therefore sought to identify the Gi/o protein-coupled receptors in cardiac myocytes (i.e. ß2-adrenergic, M2-muscarinic and A1-adenosine receptors) that are responsible for these abnormalities in heart failure by chronically administrating mice a selective antagonist of each receptor (ICI118,551, atropine and 8-cyclopentyl-1,3-dipropilxanthine (DPCPX), respectively) with isoproterenol. Compared with mice treated with isoproterenol alone, mice treated with isoproterenol plus ICI118,551 or atropine, but not DPCPX showed significantly lower lung weight/tibial length, higher fractional shortening, lower left ventricular end-diastolic pressure and higher dP/dtmax and dP/dtmin. In addition, ventricular myocytes of mice treated with isoproterenol plus ICI118,551 or atropine, but not DPCPX exhibited significantly higher TT and lower SS LTCC current densities than those of mice treated with isoproterenol alone due to normalization of the PP activities. These results indicate that ß2-adrenergic, M2-muscarinic, but not A1-adenosine receptors contribute to reduced ventricular contractility at least partially by decreasing basal TT LTCC activity in heart failure. Therefore, antagonists of ß2-adrenergic and/or M2-muscarinic receptors can be good adjuncts to ß1-adrenergic receptor antagonists in the treatment of heart failure.

The proximal C-terminus of α(1C) subunits is necessary for junctional membrane targeting of cardiac L-type calcium channels.

In cardiac myocytes, LTCCs (L-type calcium channels) form a functional signalling complex with ryanodine receptors at the JM (junctional membrane). Although the specific localization of LTCCs to the JM is critical for excitation-contraction coupling, their targeting mechanism is unclear. Transient transfection of GFP (green fluorescent protein)-α(1S) or GFP-α(1C), but not P/Q-type calcium channel α(1A), in dysgenic (α(1S)-null) GLT myotubes results in correct targeting of these LTCCs to the JMs and restoration of action-potential-induced Ca2+ transients. To identify the sequences of α(1C) responsible for JM targeting, we generated a range of α(1C)-α(1A) chimaeras, deletion mutants and alanine substitution mutants and studied their targeting properties in GLT myotubes. The results revealed that amino acids L(1681)QAGLRTL(1688) and P(1693)EIRRAIS(1700), predicted to form two adjacent α-helices in the proximal C-terminus, are necessary for the JM targeting of α(1C). The efficiency of restoration of action-potential-induced Ca2+ transients in GLT myotubes was significantly decreased by mutations in the targeting motif. JM targeting was not disrupted by the distal C-terminus of α(1C) which binds to the second α-helix. Therefore we have identified a new structural motif in the C-terminus of α(1C) that mediates the targeting of cardiac LTCCs to JMs independently of the interaction between proximal and distal C-termini of α(1C).

Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type Ca²âº channels revealed by Timothy syndrome mutation.

Dihydropyridine Ca(2+) channel antagonists (DHPs) block Ca(V)1.2 L-type Ca(2+) channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (L(I)-(II)) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba(2+) currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed- and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels' kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by L(I-II) at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the sub-threshold potential.

Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca²âº channel activity through phosphatases in heart failure.

L-type Ca(2+) channels (LTCCs) play an essential role in the excitation-contraction coupling of ventricular myocytes. We previously found that t-tubular (TT) LTCC current density was halved by the activation of protein phosphatase (PP)1 and/or PP2A, whereas surface sarcolemmal (SS) LTCC current density was increased by the inhibition of PP1 and/or PP2A activity in failing ventricular myocytes of mice chronically treated with isoproterenol (ISO mice). In the present study, we examined the possible involvement of inhibitory heterotrimeric G proteins (G(i/o)) in these abnormalities by chronically administrating pertussis toxin (PTX) to ISO mice (ISO + PTX mice). Compared with ISO mice, ISO + PTX mice exhibited significantly higher fractional shortening of the left ventricle. The expression level of Gα(i2) proteins was not altered by the treatment of mice with ISO and/or PTX. ISO + PTX myocytes had normal TT and SS LTCC current densities because they had higher and lower availability and/or open probability of TT and SS LTCCs than ISO myocytes, respectively. A selective PKA inhibitor, H-89, did not affect LTCC current densities in ISO + PTX myocytes. A selective PP2A inhibitor, fostriecin, did not affect SS or TT current density in control or ISO + PTX myocytes but significantly increased TT but not SS LTCC current density in ISO myocytes. These results indicate that chronic receptor-mediated activation of G(i/o) in vivo decreases basal TT LTCC activity by activating PP2A and increases basal SS LTCC activity by inhibiting PP1 without modulating PKA in heart failure.